Australian amp New ZealandAustralian amp New ZealandSociety of NephrologySociety of Nephrology

3-5 April 2009

The 9th Annual ANZSNPostgraduate Meeting

Philip KT LiMD FRCP FACP

Chief of Nephrology amp ConsultantHonorary Professor of Medicine

Department of Medicine and TherapeuticsPrince of Wales Hospital

Chinese University of Hong Kong

ISN 2004 Conference on

Prevention of Progression of Renal Disease June 29- July 1 2004

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Chronic Kidney Disease Renoprotection Programmes

Locate People at riskDiabetes Hypertension Elderly HIV

Initiator InjuryProtein leakage Proteinuria

Prevent ProgressionKDRP Programmes

ESRDPreparing people

TxDialysis

Peritoneal Dialysis

Prevention

Resourcesrarr

Pat

ient

s at

risk

rarr

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

325

585

90

Injuries(51 million)

Noncommunicableconditions(331 million)

WORLDDeaths by broad cause group 2001

Communicable diseases maternal and perinatal

conditions and nutritional deficiencies

(184 million)

Total deaths 56554000

Source World Health Report 2002

Yach D et al JAMA 20042912616-2622

Global Mortality From Chronic DiseasesGlobal Mortality From Chronic DiseasesChronic diseases Injuries and

Communicable diseases

In 2002 the leading chronic diseases caused 29 million deaths worldwide

Yach D et al JAMA 20042912616-2622

Global Mortality From Chronic DiseasesGlobal Mortality From Chronic DiseasesChronic diseases Injuries and

Communicable diseases

In 2002 the leading chronic diseases caused 29 million deaths worldwide

CVS

Neoplasm

OthersCOADDM

Projections of Global Mortality and BurdenProjections of Global Mortality and Burdenof Disease from 2002 to 2030of Disease from 2002 to 2030

Changes in Rankings for 15 Leading Causes of Death 2002 and 2030

Colin D Mathers Dejan LoncarEvidence and Information for Policy Cluster World Health Organization Geneva Switzerland

Mathers CD Loncar D PLoS Med 2006 Nov3(11)e442

GLOBAL MAINTENANCE DIALYSIS POPULATION FROM 1990 TO 2010

1990 2000 2010

426000

1490000

2500000

Lysaght MJ J Am Soc Nephrol 2002 13 S37-40

Incidence of ESRD 2006

Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only

USRDS 2008

1 Taiwan 4182 USA 3633 Mexico 3464 Shanghai 2825 Japan 275

22 HK 140

30 NZ 11531 Australia 115

Prevalence of ESRD 2006

Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only

1 Taiwan 22262 Japan 19563 USA 16414 Germany 1114

7 HK 994

18 NZ 77819 Australia778

USRDS 2008

Age-specific prevalence of CKD (per 100 individuals) from 1996 to 2003 and incidence (per 100 person-years) from 1997 to 2003

Kuo HW et al Am J Kidney Dis 2007 Jan49(1)46-55 Prev

alen

ce (p

er 1

00 in

divi

dual

s) I

ncid

ence

(per

100

per

son-

year

s)

Year

Incidence

75+

65-74

45-64

20-44

0-19

Odds Ratio of 1395 for ge75 years compared with lt 20 years

Epidemiological features of CKD in Taiwan Epidemiological features of CKD in Taiwan bull 200000 individuals randomly sampled from 1996 to 2003

bull The prevalence CKD increased from 199 in 1996 to 983 in 2003

bull The overall incidence rate during 1997 to 2003 was 135100 person-years

bull Age is a key predictor of CKD ndash Odds Ratio of 1395 for age ge75 years compared with age lt 20

years

bull Other risk factors of CKD ndash diabetes ndash hypertension ndash hyperlipidemiandash female sex

Kuo HW et al Am J Kidney Dis 2007 Jan49(1)46-55

NEOERICA dataNHANES data

00402lt 15 (or on dialysis)

5020215 ndash 294464330 ndash 593

3060 ndash 892

33ge 901

UK Prevalence ()

US PopulationPrevalence ()

GFR mlmin173 m2

CKDStage

Coresh J et al Am J Kidney Dis 2003 41 1-12De Lusignan S et al Fam Pract 2005 22 234-41

Lifetime cumulative risks for ESRD Lifetime cumulative risks for ESRD

Kiberd B J Am Soc Nephrol 2006 Nov17(11)2967-73

8 for black women

3 for white men

78 for black men

22 for white women

CHINA ESRD StatusCHINA ESRD Status

bull About 75000 ESRD patients in Mainland China are receiving treatment today

bull Nearly 2 million patients may be untreated

bull The rate of growth of treated ESRD patients is 10-12 per year

bull ESRD treatments are high cost

Presented in ISPD 2006 Asia Round table on Dialysis Economics from CMIA(Chinese Medical Insurance Agency)

China ESRD Growth Rate To Exceed That of Population

1150000000

1200000000

1250000000

1300000000

1350000000

1400000000

1450000000

1500000000

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Tota

l Pop

ulat

ion

0

50000

100000

150000

200000

250000

300000

350000

ESR

D P

atie

nts

Population Dialysis patients

ACTUAL PROJECTED

ESRD Patients07 per year

~10-12 per year

Population

Source amp CourtesyCMIA 2006 data

Incidence of ESRF (for 12 months ending 31032007) 1074 (164 pmp)

641697

789 798 830885

1019 1012960

1045 1040 1074

0100200300400500600700800900

100011001200

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

Incidence of ESRF on RRT

Hong Kong Renal Registry香港醫院管理局腎病註冊

Incidence of ESRD (pmp) by age 2005

USRDS 2007

0-19 20-44 45-64 65-74 gt75

No14 No 4 No 5 No 8 No 24

(Japan - no data)

No of patient on renal replacement therapy 7160 ( 1025 pmp)

Hong Kong Renal Registry香港醫院管理局腎病註冊1998rarr2008 uarr 19 times

The reasons of this growth are

ndash Global ageing

ndash Multi-morbid population

ndash Higher life-expectancy of ESRD patients

ndash Increasing access of younger people in countries in which RRT has been limited until today

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Lung Cancer

KidneyFailure

ColonCancer

BreastCancer

Prostate Cancer

57

99

4232

Kidney Failure Compared to Cancer Deaths in the US in 2000

(in Thousands)157

SEER 2003(Surveillance Epidemiology and End Results)

1200

600

0

Ten

year

med

ical

cos

ts o

f di

alys

is p

opul

atio

n$

( bill

ions

)

1981-1990 1991-2000 2001-2010

800

1000

$

$

$

PREDICTED DIALYSIS COST OF APPROXIMATELY $ 11 TRILLION$ 11 TRILLION FOR THE COMING DECADE

400

200

Lysaght MJ J Am Soc Nephrol 2002 13 S37-40

De Vecchi AF et al NDT 1999

Dialysis Cost Europe

25 - 38 times gt National Average

Prevalence of ESRD in 2004 versus economic welfare in the 75 Prevalence of ESRD in 2004 versus economic welfare in the 75 countries with the largest ESRD patient populationscountries with the largest ESRD patient populations

Grassmann A et al Nephrol Dial Transplant 2005 202587-2593

Regional ESRD distributionRegion Pop GDP ESRD

million US$ (000) Prevalence pmp

EU 380 217 790Europe 804 120 393M East 271 32 150Africa 833 10 55LAmerica 512 38 310Asia 3316 11 55Japan 127 376 1830NAmerica 310 295 1400

Moeller S et al Nephrol Dial Transplant 2002 Dec17(12)2071-6

Morelinkage

withGDP

than the general

population

China Future Dialysis Expense

￥0

￥5

￥10

￥15

￥20

￥25

￥30

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Bill

ions

Ann

ual E

xpen

ditu

re o

n D

ialy

sis

￥7143670260

￥29087632671Factors98 dialysis population growth per yearModality share remains 90 HD 10 PD

Source amp Courtesy CMIA 2006 data

(From 71 billion in 2005 to 29 billion in 2020)

TIME December 8 2003Newsweek Sept 4 2000

Percentage of incident patients

with diabetes 2006

data presented only for those countries from which relevant information was available All rates are unadjusted ^UK England Wales amp Northern Ireland (Scotland data reported separately) Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only Latest data for Canada Croatia amp Italy are for 2005 Data for France include 13 regions in 2005 amp 15 regions in 2006

1 Malaysia 5752 Mexico 4993 USA 4434 Japan 4255 Taiwan 424

8 Hong Kong 41

18 Australia 324

USRDS 2008

Diagnosis Distribution of NEW patients 2006 - 2007GN

217

Obstructive28

Unknown179

DM393

Others38

HTvascular106

Inherited cong30

Infection reflux08

新症病人之病因 (2006-7)

感染

遺傳

尿道阻塞

高血壓糖尿病

腎小球腎炎

DM 393

GN 217

Hong Kong Renal Registry香港醫院管理局腎病註冊

World

20002030

154 m370 m

55 m84 m

Developed Developing

99 m286 m

167338

329

182

524307

28391

809

228

423

186

09 16

20002030

In million subjects

102

81

71

211

255

127

78

THE GLOBAL BURDEN OF DIABETES (2000-2030)

WHO March 2003

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Consensus Workshop

Part 1 Detection of chronic kidney disease

Part 2 Evaluation and estimating progression of chronic kidney disease

Part 3 Measures to prevent the progression of chronic kidney disease

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)s2-7

Summary of the Consensus Statements (1)Summary of the Consensus Statements (1)

bull It is recommended to establish a global surveillance center (ISN Kidney Disease Data Centre or ISN KDDC) to coordinate worldwide standardized screening studies with standardized screening techniques in appropriate target groups to allow for the collection of clearly comparable data

bull It is recommended that patients diagnosed with diabetes and hypertension

should have regular screening for development of kidney disease

bull It is recommended that close relatives of patients with nephropathy due to diabetes hypertension and glomerulonephritis should also be the primary targets for screening to detect clinically silent kidney disease

bull No consensus was made on an exact age ldquocut-offrdquo for initiating CKD screening

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

SHAREScreening for Hong Kong Asymptomatic Renal

Population and Evaluation programme

普查計劃

腎康體健

Li PKT et al Kidney Int 2005 Apr(94)s36-40

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Philip KT LiMD FRCP FACP

Chief of Nephrology amp ConsultantHonorary Professor of Medicine

Department of Medicine and TherapeuticsPrince of Wales Hospital

Chinese University of Hong Kong

ISN 2004 Conference on

Prevention of Progression of Renal Disease June 29- July 1 2004

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Chronic Kidney Disease Renoprotection Programmes

Locate People at riskDiabetes Hypertension Elderly HIV

Initiator InjuryProtein leakage Proteinuria

Prevent ProgressionKDRP Programmes

ESRDPreparing people

TxDialysis

Peritoneal Dialysis

Prevention

Resourcesrarr

Pat

ient

s at

risk

rarr

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

325

585

90

Injuries(51 million)

Noncommunicableconditions(331 million)

WORLDDeaths by broad cause group 2001

Communicable diseases maternal and perinatal

conditions and nutritional deficiencies

(184 million)

Total deaths 56554000

Source World Health Report 2002

Yach D et al JAMA 20042912616-2622

Global Mortality From Chronic DiseasesGlobal Mortality From Chronic DiseasesChronic diseases Injuries and

Communicable diseases

In 2002 the leading chronic diseases caused 29 million deaths worldwide

Yach D et al JAMA 20042912616-2622

Global Mortality From Chronic DiseasesGlobal Mortality From Chronic DiseasesChronic diseases Injuries and

Communicable diseases

In 2002 the leading chronic diseases caused 29 million deaths worldwide

CVS

Neoplasm

OthersCOADDM

Projections of Global Mortality and BurdenProjections of Global Mortality and Burdenof Disease from 2002 to 2030of Disease from 2002 to 2030

Changes in Rankings for 15 Leading Causes of Death 2002 and 2030

Colin D Mathers Dejan LoncarEvidence and Information for Policy Cluster World Health Organization Geneva Switzerland

Mathers CD Loncar D PLoS Med 2006 Nov3(11)e442

GLOBAL MAINTENANCE DIALYSIS POPULATION FROM 1990 TO 2010

1990 2000 2010

426000

1490000

2500000

Lysaght MJ J Am Soc Nephrol 2002 13 S37-40

Incidence of ESRD 2006

Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only

USRDS 2008

1 Taiwan 4182 USA 3633 Mexico 3464 Shanghai 2825 Japan 275

22 HK 140

30 NZ 11531 Australia 115

Prevalence of ESRD 2006

Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only

1 Taiwan 22262 Japan 19563 USA 16414 Germany 1114

7 HK 994

18 NZ 77819 Australia778

USRDS 2008

Age-specific prevalence of CKD (per 100 individuals) from 1996 to 2003 and incidence (per 100 person-years) from 1997 to 2003

Kuo HW et al Am J Kidney Dis 2007 Jan49(1)46-55 Prev

alen

ce (p

er 1

00 in

divi

dual

s) I

ncid

ence

(per

100

per

son-

year

s)

Year

Incidence

75+

65-74

45-64

20-44

0-19

Odds Ratio of 1395 for ge75 years compared with lt 20 years

Epidemiological features of CKD in Taiwan Epidemiological features of CKD in Taiwan bull 200000 individuals randomly sampled from 1996 to 2003

bull The prevalence CKD increased from 199 in 1996 to 983 in 2003

bull The overall incidence rate during 1997 to 2003 was 135100 person-years

bull Age is a key predictor of CKD ndash Odds Ratio of 1395 for age ge75 years compared with age lt 20

years

bull Other risk factors of CKD ndash diabetes ndash hypertension ndash hyperlipidemiandash female sex

Kuo HW et al Am J Kidney Dis 2007 Jan49(1)46-55

NEOERICA dataNHANES data

00402lt 15 (or on dialysis)

5020215 ndash 294464330 ndash 593

3060 ndash 892

33ge 901

UK Prevalence ()

US PopulationPrevalence ()

GFR mlmin173 m2

CKDStage

Coresh J et al Am J Kidney Dis 2003 41 1-12De Lusignan S et al Fam Pract 2005 22 234-41

Lifetime cumulative risks for ESRD Lifetime cumulative risks for ESRD

Kiberd B J Am Soc Nephrol 2006 Nov17(11)2967-73

8 for black women

3 for white men

78 for black men

22 for white women

CHINA ESRD StatusCHINA ESRD Status

bull About 75000 ESRD patients in Mainland China are receiving treatment today

bull Nearly 2 million patients may be untreated

bull The rate of growth of treated ESRD patients is 10-12 per year

bull ESRD treatments are high cost

Presented in ISPD 2006 Asia Round table on Dialysis Economics from CMIA(Chinese Medical Insurance Agency)

China ESRD Growth Rate To Exceed That of Population

1150000000

1200000000

1250000000

1300000000

1350000000

1400000000

1450000000

1500000000

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Tota

l Pop

ulat

ion

0

50000

100000

150000

200000

250000

300000

350000

ESR

D P

atie

nts

Population Dialysis patients

ACTUAL PROJECTED

ESRD Patients07 per year

~10-12 per year

Population

Source amp CourtesyCMIA 2006 data

Incidence of ESRF (for 12 months ending 31032007) 1074 (164 pmp)

641697

789 798 830885

1019 1012960

1045 1040 1074

0100200300400500600700800900

100011001200

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

Incidence of ESRF on RRT

Hong Kong Renal Registry香港醫院管理局腎病註冊

Incidence of ESRD (pmp) by age 2005

USRDS 2007

0-19 20-44 45-64 65-74 gt75

No14 No 4 No 5 No 8 No 24

(Japan - no data)

No of patient on renal replacement therapy 7160 ( 1025 pmp)

Hong Kong Renal Registry香港醫院管理局腎病註冊1998rarr2008 uarr 19 times

The reasons of this growth are

ndash Global ageing

ndash Multi-morbid population

ndash Higher life-expectancy of ESRD patients

ndash Increasing access of younger people in countries in which RRT has been limited until today

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Lung Cancer

KidneyFailure

ColonCancer

BreastCancer

Prostate Cancer

57

99

4232

Kidney Failure Compared to Cancer Deaths in the US in 2000

(in Thousands)157

SEER 2003(Surveillance Epidemiology and End Results)

1200

600

0

Ten

year

med

ical

cos

ts o

f di

alys

is p

opul

atio

n$

( bill

ions

)

1981-1990 1991-2000 2001-2010

800

1000

$

$

$

PREDICTED DIALYSIS COST OF APPROXIMATELY $ 11 TRILLION$ 11 TRILLION FOR THE COMING DECADE

400

200

Lysaght MJ J Am Soc Nephrol 2002 13 S37-40

De Vecchi AF et al NDT 1999

Dialysis Cost Europe

25 - 38 times gt National Average

Prevalence of ESRD in 2004 versus economic welfare in the 75 Prevalence of ESRD in 2004 versus economic welfare in the 75 countries with the largest ESRD patient populationscountries with the largest ESRD patient populations

Grassmann A et al Nephrol Dial Transplant 2005 202587-2593

Regional ESRD distributionRegion Pop GDP ESRD

million US$ (000) Prevalence pmp

EU 380 217 790Europe 804 120 393M East 271 32 150Africa 833 10 55LAmerica 512 38 310Asia 3316 11 55Japan 127 376 1830NAmerica 310 295 1400

Moeller S et al Nephrol Dial Transplant 2002 Dec17(12)2071-6

Morelinkage

withGDP

than the general

population

China Future Dialysis Expense

￥0

￥5

￥10

￥15

￥20

￥25

￥30

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Bill

ions

Ann

ual E

xpen

ditu

re o

n D

ialy

sis

￥7143670260

￥29087632671Factors98 dialysis population growth per yearModality share remains 90 HD 10 PD

Source amp Courtesy CMIA 2006 data

(From 71 billion in 2005 to 29 billion in 2020)

TIME December 8 2003Newsweek Sept 4 2000

Percentage of incident patients

with diabetes 2006

data presented only for those countries from which relevant information was available All rates are unadjusted ^UK England Wales amp Northern Ireland (Scotland data reported separately) Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only Latest data for Canada Croatia amp Italy are for 2005 Data for France include 13 regions in 2005 amp 15 regions in 2006

1 Malaysia 5752 Mexico 4993 USA 4434 Japan 4255 Taiwan 424

8 Hong Kong 41

18 Australia 324

USRDS 2008

Diagnosis Distribution of NEW patients 2006 - 2007GN

217

Obstructive28

Unknown179

DM393

Others38

HTvascular106

Inherited cong30

Infection reflux08

新症病人之病因 (2006-7)

感染

遺傳

尿道阻塞

高血壓糖尿病

腎小球腎炎

DM 393

GN 217

Hong Kong Renal Registry香港醫院管理局腎病註冊

World

20002030

154 m370 m

55 m84 m

Developed Developing

99 m286 m

167338

329

182

524307

28391

809

228

423

186

09 16

20002030

In million subjects

102

81

71

211

255

127

78

THE GLOBAL BURDEN OF DIABETES (2000-2030)

WHO March 2003

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Consensus Workshop

Part 1 Detection of chronic kidney disease

Part 2 Evaluation and estimating progression of chronic kidney disease

Part 3 Measures to prevent the progression of chronic kidney disease

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)s2-7

Summary of the Consensus Statements (1)Summary of the Consensus Statements (1)

bull It is recommended to establish a global surveillance center (ISN Kidney Disease Data Centre or ISN KDDC) to coordinate worldwide standardized screening studies with standardized screening techniques in appropriate target groups to allow for the collection of clearly comparable data

bull It is recommended that patients diagnosed with diabetes and hypertension

should have regular screening for development of kidney disease

bull It is recommended that close relatives of patients with nephropathy due to diabetes hypertension and glomerulonephritis should also be the primary targets for screening to detect clinically silent kidney disease

bull No consensus was made on an exact age ldquocut-offrdquo for initiating CKD screening

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

SHAREScreening for Hong Kong Asymptomatic Renal

Population and Evaluation programme

普查計劃

腎康體健

Li PKT et al Kidney Int 2005 Apr(94)s36-40

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

ISN 2004 Conference on

Prevention of Progression of Renal Disease June 29- July 1 2004

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Chronic Kidney Disease Renoprotection Programmes

Locate People at riskDiabetes Hypertension Elderly HIV

Initiator InjuryProtein leakage Proteinuria

Prevent ProgressionKDRP Programmes

ESRDPreparing people

TxDialysis

Peritoneal Dialysis

Prevention

Resourcesrarr

Pat

ient

s at

risk

rarr

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

325

585

90

Injuries(51 million)

Noncommunicableconditions(331 million)

WORLDDeaths by broad cause group 2001

Communicable diseases maternal and perinatal

conditions and nutritional deficiencies

(184 million)

Total deaths 56554000

Source World Health Report 2002

Yach D et al JAMA 20042912616-2622

Global Mortality From Chronic DiseasesGlobal Mortality From Chronic DiseasesChronic diseases Injuries and

Communicable diseases

In 2002 the leading chronic diseases caused 29 million deaths worldwide

Yach D et al JAMA 20042912616-2622

Global Mortality From Chronic DiseasesGlobal Mortality From Chronic DiseasesChronic diseases Injuries and

Communicable diseases

In 2002 the leading chronic diseases caused 29 million deaths worldwide

CVS

Neoplasm

OthersCOADDM

Projections of Global Mortality and BurdenProjections of Global Mortality and Burdenof Disease from 2002 to 2030of Disease from 2002 to 2030

Changes in Rankings for 15 Leading Causes of Death 2002 and 2030

Colin D Mathers Dejan LoncarEvidence and Information for Policy Cluster World Health Organization Geneva Switzerland

Mathers CD Loncar D PLoS Med 2006 Nov3(11)e442

GLOBAL MAINTENANCE DIALYSIS POPULATION FROM 1990 TO 2010

1990 2000 2010

426000

1490000

2500000

Lysaght MJ J Am Soc Nephrol 2002 13 S37-40

Incidence of ESRD 2006

Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only

USRDS 2008

1 Taiwan 4182 USA 3633 Mexico 3464 Shanghai 2825 Japan 275

22 HK 140

30 NZ 11531 Australia 115

Prevalence of ESRD 2006

Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only

1 Taiwan 22262 Japan 19563 USA 16414 Germany 1114

7 HK 994

18 NZ 77819 Australia778

USRDS 2008

Age-specific prevalence of CKD (per 100 individuals) from 1996 to 2003 and incidence (per 100 person-years) from 1997 to 2003

Kuo HW et al Am J Kidney Dis 2007 Jan49(1)46-55 Prev

alen

ce (p

er 1

00 in

divi

dual

s) I

ncid

ence

(per

100

per

son-

year

s)

Year

Incidence

75+

65-74

45-64

20-44

0-19

Odds Ratio of 1395 for ge75 years compared with lt 20 years

Epidemiological features of CKD in Taiwan Epidemiological features of CKD in Taiwan bull 200000 individuals randomly sampled from 1996 to 2003

bull The prevalence CKD increased from 199 in 1996 to 983 in 2003

bull The overall incidence rate during 1997 to 2003 was 135100 person-years

bull Age is a key predictor of CKD ndash Odds Ratio of 1395 for age ge75 years compared with age lt 20

years

bull Other risk factors of CKD ndash diabetes ndash hypertension ndash hyperlipidemiandash female sex

Kuo HW et al Am J Kidney Dis 2007 Jan49(1)46-55

NEOERICA dataNHANES data

00402lt 15 (or on dialysis)

5020215 ndash 294464330 ndash 593

3060 ndash 892

33ge 901

UK Prevalence ()

US PopulationPrevalence ()

GFR mlmin173 m2

CKDStage

Coresh J et al Am J Kidney Dis 2003 41 1-12De Lusignan S et al Fam Pract 2005 22 234-41

Lifetime cumulative risks for ESRD Lifetime cumulative risks for ESRD

Kiberd B J Am Soc Nephrol 2006 Nov17(11)2967-73

8 for black women

3 for white men

78 for black men

22 for white women

CHINA ESRD StatusCHINA ESRD Status

bull About 75000 ESRD patients in Mainland China are receiving treatment today

bull Nearly 2 million patients may be untreated

bull The rate of growth of treated ESRD patients is 10-12 per year

bull ESRD treatments are high cost

Presented in ISPD 2006 Asia Round table on Dialysis Economics from CMIA(Chinese Medical Insurance Agency)

China ESRD Growth Rate To Exceed That of Population

1150000000

1200000000

1250000000

1300000000

1350000000

1400000000

1450000000

1500000000

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Tota

l Pop

ulat

ion

0

50000

100000

150000

200000

250000

300000

350000

ESR

D P

atie

nts

Population Dialysis patients

ACTUAL PROJECTED

ESRD Patients07 per year

~10-12 per year

Population

Source amp CourtesyCMIA 2006 data

Incidence of ESRF (for 12 months ending 31032007) 1074 (164 pmp)

641697

789 798 830885

1019 1012960

1045 1040 1074

0100200300400500600700800900

100011001200

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

Incidence of ESRF on RRT

Hong Kong Renal Registry香港醫院管理局腎病註冊

Incidence of ESRD (pmp) by age 2005

USRDS 2007

0-19 20-44 45-64 65-74 gt75

No14 No 4 No 5 No 8 No 24

(Japan - no data)

No of patient on renal replacement therapy 7160 ( 1025 pmp)

Hong Kong Renal Registry香港醫院管理局腎病註冊1998rarr2008 uarr 19 times

The reasons of this growth are

ndash Global ageing

ndash Multi-morbid population

ndash Higher life-expectancy of ESRD patients

ndash Increasing access of younger people in countries in which RRT has been limited until today

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Lung Cancer

KidneyFailure

ColonCancer

BreastCancer

Prostate Cancer

57

99

4232

Kidney Failure Compared to Cancer Deaths in the US in 2000

(in Thousands)157

SEER 2003(Surveillance Epidemiology and End Results)

1200

600

0

Ten

year

med

ical

cos

ts o

f di

alys

is p

opul

atio

n$

( bill

ions

)

1981-1990 1991-2000 2001-2010

800

1000

$

$

$

PREDICTED DIALYSIS COST OF APPROXIMATELY $ 11 TRILLION$ 11 TRILLION FOR THE COMING DECADE

400

200

Lysaght MJ J Am Soc Nephrol 2002 13 S37-40

De Vecchi AF et al NDT 1999

Dialysis Cost Europe

25 - 38 times gt National Average

Prevalence of ESRD in 2004 versus economic welfare in the 75 Prevalence of ESRD in 2004 versus economic welfare in the 75 countries with the largest ESRD patient populationscountries with the largest ESRD patient populations

Grassmann A et al Nephrol Dial Transplant 2005 202587-2593

Regional ESRD distributionRegion Pop GDP ESRD

million US$ (000) Prevalence pmp

EU 380 217 790Europe 804 120 393M East 271 32 150Africa 833 10 55LAmerica 512 38 310Asia 3316 11 55Japan 127 376 1830NAmerica 310 295 1400

Moeller S et al Nephrol Dial Transplant 2002 Dec17(12)2071-6

Morelinkage

withGDP

than the general

population

China Future Dialysis Expense

￥0

￥5

￥10

￥15

￥20

￥25

￥30

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Bill

ions

Ann

ual E

xpen

ditu

re o

n D

ialy

sis

￥7143670260

￥29087632671Factors98 dialysis population growth per yearModality share remains 90 HD 10 PD

Source amp Courtesy CMIA 2006 data

(From 71 billion in 2005 to 29 billion in 2020)

TIME December 8 2003Newsweek Sept 4 2000

Percentage of incident patients

with diabetes 2006

data presented only for those countries from which relevant information was available All rates are unadjusted ^UK England Wales amp Northern Ireland (Scotland data reported separately) Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only Latest data for Canada Croatia amp Italy are for 2005 Data for France include 13 regions in 2005 amp 15 regions in 2006

1 Malaysia 5752 Mexico 4993 USA 4434 Japan 4255 Taiwan 424

8 Hong Kong 41

18 Australia 324

USRDS 2008

Diagnosis Distribution of NEW patients 2006 - 2007GN

217

Obstructive28

Unknown179

DM393

Others38

HTvascular106

Inherited cong30

Infection reflux08

新症病人之病因 (2006-7)

感染

遺傳

尿道阻塞

高血壓糖尿病

腎小球腎炎

DM 393

GN 217

Hong Kong Renal Registry香港醫院管理局腎病註冊

World

20002030

154 m370 m

55 m84 m

Developed Developing

99 m286 m

167338

329

182

524307

28391

809

228

423

186

09 16

20002030

In million subjects

102

81

71

211

255

127

78

THE GLOBAL BURDEN OF DIABETES (2000-2030)

WHO March 2003

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Consensus Workshop

Part 1 Detection of chronic kidney disease

Part 2 Evaluation and estimating progression of chronic kidney disease

Part 3 Measures to prevent the progression of chronic kidney disease

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)s2-7

Summary of the Consensus Statements (1)Summary of the Consensus Statements (1)

bull It is recommended to establish a global surveillance center (ISN Kidney Disease Data Centre or ISN KDDC) to coordinate worldwide standardized screening studies with standardized screening techniques in appropriate target groups to allow for the collection of clearly comparable data

bull It is recommended that patients diagnosed with diabetes and hypertension

should have regular screening for development of kidney disease

bull It is recommended that close relatives of patients with nephropathy due to diabetes hypertension and glomerulonephritis should also be the primary targets for screening to detect clinically silent kidney disease

bull No consensus was made on an exact age ldquocut-offrdquo for initiating CKD screening

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

SHAREScreening for Hong Kong Asymptomatic Renal

Population and Evaluation programme

普查計劃

腎康體健

Li PKT et al Kidney Int 2005 Apr(94)s36-40

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Chronic Kidney Disease Renoprotection Programmes

Locate People at riskDiabetes Hypertension Elderly HIV

Initiator InjuryProtein leakage Proteinuria

Prevent ProgressionKDRP Programmes

ESRDPreparing people

TxDialysis

Peritoneal Dialysis

Prevention

Resourcesrarr

Pat

ient

s at

risk

rarr

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

325

585

90

Injuries(51 million)

Noncommunicableconditions(331 million)

WORLDDeaths by broad cause group 2001

Communicable diseases maternal and perinatal

conditions and nutritional deficiencies

(184 million)

Total deaths 56554000

Source World Health Report 2002

Yach D et al JAMA 20042912616-2622

Global Mortality From Chronic DiseasesGlobal Mortality From Chronic DiseasesChronic diseases Injuries and

Communicable diseases

In 2002 the leading chronic diseases caused 29 million deaths worldwide

Yach D et al JAMA 20042912616-2622

Global Mortality From Chronic DiseasesGlobal Mortality From Chronic DiseasesChronic diseases Injuries and

Communicable diseases

In 2002 the leading chronic diseases caused 29 million deaths worldwide

CVS

Neoplasm

OthersCOADDM

Projections of Global Mortality and BurdenProjections of Global Mortality and Burdenof Disease from 2002 to 2030of Disease from 2002 to 2030

Changes in Rankings for 15 Leading Causes of Death 2002 and 2030

Colin D Mathers Dejan LoncarEvidence and Information for Policy Cluster World Health Organization Geneva Switzerland

Mathers CD Loncar D PLoS Med 2006 Nov3(11)e442

GLOBAL MAINTENANCE DIALYSIS POPULATION FROM 1990 TO 2010

1990 2000 2010

426000

1490000

2500000

Lysaght MJ J Am Soc Nephrol 2002 13 S37-40

Incidence of ESRD 2006

Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only

USRDS 2008

1 Taiwan 4182 USA 3633 Mexico 3464 Shanghai 2825 Japan 275

22 HK 140

30 NZ 11531 Australia 115

Prevalence of ESRD 2006

Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only

1 Taiwan 22262 Japan 19563 USA 16414 Germany 1114

7 HK 994

18 NZ 77819 Australia778

USRDS 2008

Age-specific prevalence of CKD (per 100 individuals) from 1996 to 2003 and incidence (per 100 person-years) from 1997 to 2003

Kuo HW et al Am J Kidney Dis 2007 Jan49(1)46-55 Prev

alen

ce (p

er 1

00 in

divi

dual

s) I

ncid

ence

(per

100

per

son-

year

s)

Year

Incidence

75+

65-74

45-64

20-44

0-19

Odds Ratio of 1395 for ge75 years compared with lt 20 years

Epidemiological features of CKD in Taiwan Epidemiological features of CKD in Taiwan bull 200000 individuals randomly sampled from 1996 to 2003

bull The prevalence CKD increased from 199 in 1996 to 983 in 2003

bull The overall incidence rate during 1997 to 2003 was 135100 person-years

bull Age is a key predictor of CKD ndash Odds Ratio of 1395 for age ge75 years compared with age lt 20

years

bull Other risk factors of CKD ndash diabetes ndash hypertension ndash hyperlipidemiandash female sex

Kuo HW et al Am J Kidney Dis 2007 Jan49(1)46-55

NEOERICA dataNHANES data

00402lt 15 (or on dialysis)

5020215 ndash 294464330 ndash 593

3060 ndash 892

33ge 901

UK Prevalence ()

US PopulationPrevalence ()

GFR mlmin173 m2

CKDStage

Coresh J et al Am J Kidney Dis 2003 41 1-12De Lusignan S et al Fam Pract 2005 22 234-41

Lifetime cumulative risks for ESRD Lifetime cumulative risks for ESRD

Kiberd B J Am Soc Nephrol 2006 Nov17(11)2967-73

8 for black women

3 for white men

78 for black men

22 for white women

CHINA ESRD StatusCHINA ESRD Status

bull About 75000 ESRD patients in Mainland China are receiving treatment today

bull Nearly 2 million patients may be untreated

bull The rate of growth of treated ESRD patients is 10-12 per year

bull ESRD treatments are high cost

Presented in ISPD 2006 Asia Round table on Dialysis Economics from CMIA(Chinese Medical Insurance Agency)

China ESRD Growth Rate To Exceed That of Population

1150000000

1200000000

1250000000

1300000000

1350000000

1400000000

1450000000

1500000000

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Tota

l Pop

ulat

ion

0

50000

100000

150000

200000

250000

300000

350000

ESR

D P

atie

nts

Population Dialysis patients

ACTUAL PROJECTED

ESRD Patients07 per year

~10-12 per year

Population

Source amp CourtesyCMIA 2006 data

Incidence of ESRF (for 12 months ending 31032007) 1074 (164 pmp)

641697

789 798 830885

1019 1012960

1045 1040 1074

0100200300400500600700800900

100011001200

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

Incidence of ESRF on RRT

Hong Kong Renal Registry香港醫院管理局腎病註冊

Incidence of ESRD (pmp) by age 2005

USRDS 2007

0-19 20-44 45-64 65-74 gt75

No14 No 4 No 5 No 8 No 24

(Japan - no data)

No of patient on renal replacement therapy 7160 ( 1025 pmp)

Hong Kong Renal Registry香港醫院管理局腎病註冊1998rarr2008 uarr 19 times

The reasons of this growth are

ndash Global ageing

ndash Multi-morbid population

ndash Higher life-expectancy of ESRD patients

ndash Increasing access of younger people in countries in which RRT has been limited until today

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Lung Cancer

KidneyFailure

ColonCancer

BreastCancer

Prostate Cancer

57

99

4232

Kidney Failure Compared to Cancer Deaths in the US in 2000

(in Thousands)157

SEER 2003(Surveillance Epidemiology and End Results)

1200

600

0

Ten

year

med

ical

cos

ts o

f di

alys

is p

opul

atio

n$

( bill

ions

)

1981-1990 1991-2000 2001-2010

800

1000

$

$

$

PREDICTED DIALYSIS COST OF APPROXIMATELY $ 11 TRILLION$ 11 TRILLION FOR THE COMING DECADE

400

200

Lysaght MJ J Am Soc Nephrol 2002 13 S37-40

De Vecchi AF et al NDT 1999

Dialysis Cost Europe

25 - 38 times gt National Average

Prevalence of ESRD in 2004 versus economic welfare in the 75 Prevalence of ESRD in 2004 versus economic welfare in the 75 countries with the largest ESRD patient populationscountries with the largest ESRD patient populations

Grassmann A et al Nephrol Dial Transplant 2005 202587-2593

Regional ESRD distributionRegion Pop GDP ESRD

million US$ (000) Prevalence pmp

EU 380 217 790Europe 804 120 393M East 271 32 150Africa 833 10 55LAmerica 512 38 310Asia 3316 11 55Japan 127 376 1830NAmerica 310 295 1400

Moeller S et al Nephrol Dial Transplant 2002 Dec17(12)2071-6

Morelinkage

withGDP

than the general

population

China Future Dialysis Expense

￥0

￥5

￥10

￥15

￥20

￥25

￥30

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Bill

ions

Ann

ual E

xpen

ditu

re o

n D

ialy

sis

￥7143670260

￥29087632671Factors98 dialysis population growth per yearModality share remains 90 HD 10 PD

Source amp Courtesy CMIA 2006 data

(From 71 billion in 2005 to 29 billion in 2020)

TIME December 8 2003Newsweek Sept 4 2000

Percentage of incident patients

with diabetes 2006

data presented only for those countries from which relevant information was available All rates are unadjusted ^UK England Wales amp Northern Ireland (Scotland data reported separately) Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only Latest data for Canada Croatia amp Italy are for 2005 Data for France include 13 regions in 2005 amp 15 regions in 2006

1 Malaysia 5752 Mexico 4993 USA 4434 Japan 4255 Taiwan 424

8 Hong Kong 41

18 Australia 324

USRDS 2008

Diagnosis Distribution of NEW patients 2006 - 2007GN

217

Obstructive28

Unknown179

DM393

Others38

HTvascular106

Inherited cong30

Infection reflux08

新症病人之病因 (2006-7)

感染

遺傳

尿道阻塞

高血壓糖尿病

腎小球腎炎

DM 393

GN 217

Hong Kong Renal Registry香港醫院管理局腎病註冊

World

20002030

154 m370 m

55 m84 m

Developed Developing

99 m286 m

167338

329

182

524307

28391

809

228

423

186

09 16

20002030

In million subjects

102

81

71

211

255

127

78

THE GLOBAL BURDEN OF DIABETES (2000-2030)

WHO March 2003

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Consensus Workshop

Part 1 Detection of chronic kidney disease

Part 2 Evaluation and estimating progression of chronic kidney disease

Part 3 Measures to prevent the progression of chronic kidney disease

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)s2-7

Summary of the Consensus Statements (1)Summary of the Consensus Statements (1)

bull It is recommended to establish a global surveillance center (ISN Kidney Disease Data Centre or ISN KDDC) to coordinate worldwide standardized screening studies with standardized screening techniques in appropriate target groups to allow for the collection of clearly comparable data

bull It is recommended that patients diagnosed with diabetes and hypertension

should have regular screening for development of kidney disease

bull It is recommended that close relatives of patients with nephropathy due to diabetes hypertension and glomerulonephritis should also be the primary targets for screening to detect clinically silent kidney disease

bull No consensus was made on an exact age ldquocut-offrdquo for initiating CKD screening

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

SHAREScreening for Hong Kong Asymptomatic Renal

Population and Evaluation programme

普查計劃

腎康體健

Li PKT et al Kidney Int 2005 Apr(94)s36-40

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Chronic Kidney Disease Renoprotection Programmes

Locate People at riskDiabetes Hypertension Elderly HIV

Initiator InjuryProtein leakage Proteinuria

Prevent ProgressionKDRP Programmes

ESRDPreparing people

TxDialysis

Peritoneal Dialysis

Prevention

Resourcesrarr

Pat

ient

s at

risk

rarr

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

325

585

90

Injuries(51 million)

Noncommunicableconditions(331 million)

WORLDDeaths by broad cause group 2001

Communicable diseases maternal and perinatal

conditions and nutritional deficiencies

(184 million)

Total deaths 56554000

Source World Health Report 2002

Yach D et al JAMA 20042912616-2622

Global Mortality From Chronic DiseasesGlobal Mortality From Chronic DiseasesChronic diseases Injuries and

Communicable diseases

In 2002 the leading chronic diseases caused 29 million deaths worldwide

Yach D et al JAMA 20042912616-2622

Global Mortality From Chronic DiseasesGlobal Mortality From Chronic DiseasesChronic diseases Injuries and

Communicable diseases

In 2002 the leading chronic diseases caused 29 million deaths worldwide

CVS

Neoplasm

OthersCOADDM

Projections of Global Mortality and BurdenProjections of Global Mortality and Burdenof Disease from 2002 to 2030of Disease from 2002 to 2030

Changes in Rankings for 15 Leading Causes of Death 2002 and 2030

Colin D Mathers Dejan LoncarEvidence and Information for Policy Cluster World Health Organization Geneva Switzerland

Mathers CD Loncar D PLoS Med 2006 Nov3(11)e442

GLOBAL MAINTENANCE DIALYSIS POPULATION FROM 1990 TO 2010

1990 2000 2010

426000

1490000

2500000

Lysaght MJ J Am Soc Nephrol 2002 13 S37-40

Incidence of ESRD 2006

Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only

USRDS 2008

1 Taiwan 4182 USA 3633 Mexico 3464 Shanghai 2825 Japan 275

22 HK 140

30 NZ 11531 Australia 115

Prevalence of ESRD 2006

Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only

1 Taiwan 22262 Japan 19563 USA 16414 Germany 1114

7 HK 994

18 NZ 77819 Australia778

USRDS 2008

Age-specific prevalence of CKD (per 100 individuals) from 1996 to 2003 and incidence (per 100 person-years) from 1997 to 2003

Kuo HW et al Am J Kidney Dis 2007 Jan49(1)46-55 Prev

alen

ce (p

er 1

00 in

divi

dual

s) I

ncid

ence

(per

100

per

son-

year

s)

Year

Incidence

75+

65-74

45-64

20-44

0-19

Odds Ratio of 1395 for ge75 years compared with lt 20 years

Epidemiological features of CKD in Taiwan Epidemiological features of CKD in Taiwan bull 200000 individuals randomly sampled from 1996 to 2003

bull The prevalence CKD increased from 199 in 1996 to 983 in 2003

bull The overall incidence rate during 1997 to 2003 was 135100 person-years

bull Age is a key predictor of CKD ndash Odds Ratio of 1395 for age ge75 years compared with age lt 20

years

bull Other risk factors of CKD ndash diabetes ndash hypertension ndash hyperlipidemiandash female sex

Kuo HW et al Am J Kidney Dis 2007 Jan49(1)46-55

NEOERICA dataNHANES data

00402lt 15 (or on dialysis)

5020215 ndash 294464330 ndash 593

3060 ndash 892

33ge 901

UK Prevalence ()

US PopulationPrevalence ()

GFR mlmin173 m2

CKDStage

Coresh J et al Am J Kidney Dis 2003 41 1-12De Lusignan S et al Fam Pract 2005 22 234-41

Lifetime cumulative risks for ESRD Lifetime cumulative risks for ESRD

Kiberd B J Am Soc Nephrol 2006 Nov17(11)2967-73

8 for black women

3 for white men

78 for black men

22 for white women

CHINA ESRD StatusCHINA ESRD Status

bull About 75000 ESRD patients in Mainland China are receiving treatment today

bull Nearly 2 million patients may be untreated

bull The rate of growth of treated ESRD patients is 10-12 per year

bull ESRD treatments are high cost

Presented in ISPD 2006 Asia Round table on Dialysis Economics from CMIA(Chinese Medical Insurance Agency)

China ESRD Growth Rate To Exceed That of Population

1150000000

1200000000

1250000000

1300000000

1350000000

1400000000

1450000000

1500000000

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Tota

l Pop

ulat

ion

0

50000

100000

150000

200000

250000

300000

350000

ESR

D P

atie

nts

Population Dialysis patients

ACTUAL PROJECTED

ESRD Patients07 per year

~10-12 per year

Population

Source amp CourtesyCMIA 2006 data

Incidence of ESRF (for 12 months ending 31032007) 1074 (164 pmp)

641697

789 798 830885

1019 1012960

1045 1040 1074

0100200300400500600700800900

100011001200

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

Incidence of ESRF on RRT

Hong Kong Renal Registry香港醫院管理局腎病註冊

Incidence of ESRD (pmp) by age 2005

USRDS 2007

0-19 20-44 45-64 65-74 gt75

No14 No 4 No 5 No 8 No 24

(Japan - no data)

No of patient on renal replacement therapy 7160 ( 1025 pmp)

Hong Kong Renal Registry香港醫院管理局腎病註冊1998rarr2008 uarr 19 times

The reasons of this growth are

ndash Global ageing

ndash Multi-morbid population

ndash Higher life-expectancy of ESRD patients

ndash Increasing access of younger people in countries in which RRT has been limited until today

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Lung Cancer

KidneyFailure

ColonCancer

BreastCancer

Prostate Cancer

57

99

4232

Kidney Failure Compared to Cancer Deaths in the US in 2000

(in Thousands)157

SEER 2003(Surveillance Epidemiology and End Results)

1200

600

0

Ten

year

med

ical

cos

ts o

f di

alys

is p

opul

atio

n$

( bill

ions

)

1981-1990 1991-2000 2001-2010

800

1000

$

$

$

PREDICTED DIALYSIS COST OF APPROXIMATELY $ 11 TRILLION$ 11 TRILLION FOR THE COMING DECADE

400

200

Lysaght MJ J Am Soc Nephrol 2002 13 S37-40

De Vecchi AF et al NDT 1999

Dialysis Cost Europe

25 - 38 times gt National Average

Prevalence of ESRD in 2004 versus economic welfare in the 75 Prevalence of ESRD in 2004 versus economic welfare in the 75 countries with the largest ESRD patient populationscountries with the largest ESRD patient populations

Grassmann A et al Nephrol Dial Transplant 2005 202587-2593

Regional ESRD distributionRegion Pop GDP ESRD

million US$ (000) Prevalence pmp

EU 380 217 790Europe 804 120 393M East 271 32 150Africa 833 10 55LAmerica 512 38 310Asia 3316 11 55Japan 127 376 1830NAmerica 310 295 1400

Moeller S et al Nephrol Dial Transplant 2002 Dec17(12)2071-6

Morelinkage

withGDP

than the general

population

China Future Dialysis Expense

￥0

￥5

￥10

￥15

￥20

￥25

￥30

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Bill

ions

Ann

ual E

xpen

ditu

re o

n D

ialy

sis

￥7143670260

￥29087632671Factors98 dialysis population growth per yearModality share remains 90 HD 10 PD

Source amp Courtesy CMIA 2006 data

(From 71 billion in 2005 to 29 billion in 2020)

TIME December 8 2003Newsweek Sept 4 2000

Percentage of incident patients

with diabetes 2006

data presented only for those countries from which relevant information was available All rates are unadjusted ^UK England Wales amp Northern Ireland (Scotland data reported separately) Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only Latest data for Canada Croatia amp Italy are for 2005 Data for France include 13 regions in 2005 amp 15 regions in 2006

1 Malaysia 5752 Mexico 4993 USA 4434 Japan 4255 Taiwan 424

8 Hong Kong 41

18 Australia 324

USRDS 2008

Diagnosis Distribution of NEW patients 2006 - 2007GN

217

Obstructive28

Unknown179

DM393

Others38

HTvascular106

Inherited cong30

Infection reflux08

新症病人之病因 (2006-7)

感染

遺傳

尿道阻塞

高血壓糖尿病

腎小球腎炎

DM 393

GN 217

Hong Kong Renal Registry香港醫院管理局腎病註冊

World

20002030

154 m370 m

55 m84 m

Developed Developing

99 m286 m

167338

329

182

524307

28391

809

228

423

186

09 16

20002030

In million subjects

102

81

71

211

255

127

78

THE GLOBAL BURDEN OF DIABETES (2000-2030)

WHO March 2003

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Consensus Workshop

Part 1 Detection of chronic kidney disease

Part 2 Evaluation and estimating progression of chronic kidney disease

Part 3 Measures to prevent the progression of chronic kidney disease

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)s2-7

Summary of the Consensus Statements (1)Summary of the Consensus Statements (1)

bull It is recommended to establish a global surveillance center (ISN Kidney Disease Data Centre or ISN KDDC) to coordinate worldwide standardized screening studies with standardized screening techniques in appropriate target groups to allow for the collection of clearly comparable data

bull It is recommended that patients diagnosed with diabetes and hypertension

should have regular screening for development of kidney disease

bull It is recommended that close relatives of patients with nephropathy due to diabetes hypertension and glomerulonephritis should also be the primary targets for screening to detect clinically silent kidney disease

bull No consensus was made on an exact age ldquocut-offrdquo for initiating CKD screening

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

SHAREScreening for Hong Kong Asymptomatic Renal

Population and Evaluation programme

普查計劃

腎康體健

Li PKT et al Kidney Int 2005 Apr(94)s36-40

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

325

585

90

Injuries(51 million)

Noncommunicableconditions(331 million)

WORLDDeaths by broad cause group 2001

Communicable diseases maternal and perinatal

conditions and nutritional deficiencies

(184 million)

Total deaths 56554000

Source World Health Report 2002

Yach D et al JAMA 20042912616-2622

Global Mortality From Chronic DiseasesGlobal Mortality From Chronic DiseasesChronic diseases Injuries and

Communicable diseases

In 2002 the leading chronic diseases caused 29 million deaths worldwide

Yach D et al JAMA 20042912616-2622

Global Mortality From Chronic DiseasesGlobal Mortality From Chronic DiseasesChronic diseases Injuries and

Communicable diseases

In 2002 the leading chronic diseases caused 29 million deaths worldwide

CVS

Neoplasm

OthersCOADDM

Projections of Global Mortality and BurdenProjections of Global Mortality and Burdenof Disease from 2002 to 2030of Disease from 2002 to 2030

Changes in Rankings for 15 Leading Causes of Death 2002 and 2030

Colin D Mathers Dejan LoncarEvidence and Information for Policy Cluster World Health Organization Geneva Switzerland

Mathers CD Loncar D PLoS Med 2006 Nov3(11)e442

GLOBAL MAINTENANCE DIALYSIS POPULATION FROM 1990 TO 2010

1990 2000 2010

426000

1490000

2500000

Lysaght MJ J Am Soc Nephrol 2002 13 S37-40

Incidence of ESRD 2006

Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only

USRDS 2008

1 Taiwan 4182 USA 3633 Mexico 3464 Shanghai 2825 Japan 275

22 HK 140

30 NZ 11531 Australia 115

Prevalence of ESRD 2006

Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only

1 Taiwan 22262 Japan 19563 USA 16414 Germany 1114

7 HK 994

18 NZ 77819 Australia778

USRDS 2008

Age-specific prevalence of CKD (per 100 individuals) from 1996 to 2003 and incidence (per 100 person-years) from 1997 to 2003

Kuo HW et al Am J Kidney Dis 2007 Jan49(1)46-55 Prev

alen

ce (p

er 1

00 in

divi

dual

s) I

ncid

ence

(per

100

per

son-

year

s)

Year

Incidence

75+

65-74

45-64

20-44

0-19

Odds Ratio of 1395 for ge75 years compared with lt 20 years

Epidemiological features of CKD in Taiwan Epidemiological features of CKD in Taiwan bull 200000 individuals randomly sampled from 1996 to 2003

bull The prevalence CKD increased from 199 in 1996 to 983 in 2003

bull The overall incidence rate during 1997 to 2003 was 135100 person-years

bull Age is a key predictor of CKD ndash Odds Ratio of 1395 for age ge75 years compared with age lt 20

years

bull Other risk factors of CKD ndash diabetes ndash hypertension ndash hyperlipidemiandash female sex

Kuo HW et al Am J Kidney Dis 2007 Jan49(1)46-55

NEOERICA dataNHANES data

00402lt 15 (or on dialysis)

5020215 ndash 294464330 ndash 593

3060 ndash 892

33ge 901

UK Prevalence ()

US PopulationPrevalence ()

GFR mlmin173 m2

CKDStage

Coresh J et al Am J Kidney Dis 2003 41 1-12De Lusignan S et al Fam Pract 2005 22 234-41

Lifetime cumulative risks for ESRD Lifetime cumulative risks for ESRD

Kiberd B J Am Soc Nephrol 2006 Nov17(11)2967-73

8 for black women

3 for white men

78 for black men

22 for white women

CHINA ESRD StatusCHINA ESRD Status

bull About 75000 ESRD patients in Mainland China are receiving treatment today

bull Nearly 2 million patients may be untreated

bull The rate of growth of treated ESRD patients is 10-12 per year

bull ESRD treatments are high cost

Presented in ISPD 2006 Asia Round table on Dialysis Economics from CMIA(Chinese Medical Insurance Agency)

China ESRD Growth Rate To Exceed That of Population

1150000000

1200000000

1250000000

1300000000

1350000000

1400000000

1450000000

1500000000

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Tota

l Pop

ulat

ion

0

50000

100000

150000

200000

250000

300000

350000

ESR

D P

atie

nts

Population Dialysis patients

ACTUAL PROJECTED

ESRD Patients07 per year

~10-12 per year

Population

Source amp CourtesyCMIA 2006 data

Incidence of ESRF (for 12 months ending 31032007) 1074 (164 pmp)

641697

789 798 830885

1019 1012960

1045 1040 1074

0100200300400500600700800900

100011001200

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

Incidence of ESRF on RRT

Hong Kong Renal Registry香港醫院管理局腎病註冊

Incidence of ESRD (pmp) by age 2005

USRDS 2007

0-19 20-44 45-64 65-74 gt75

No14 No 4 No 5 No 8 No 24

(Japan - no data)

No of patient on renal replacement therapy 7160 ( 1025 pmp)

Hong Kong Renal Registry香港醫院管理局腎病註冊1998rarr2008 uarr 19 times

The reasons of this growth are

ndash Global ageing

ndash Multi-morbid population

ndash Higher life-expectancy of ESRD patients

ndash Increasing access of younger people in countries in which RRT has been limited until today

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Lung Cancer

KidneyFailure

ColonCancer

BreastCancer

Prostate Cancer

57

99

4232

Kidney Failure Compared to Cancer Deaths in the US in 2000

(in Thousands)157

SEER 2003(Surveillance Epidemiology and End Results)

1200

600

0

Ten

year

med

ical

cos

ts o

f di

alys

is p

opul

atio

n$

( bill

ions

)

1981-1990 1991-2000 2001-2010

800

1000

$

$

$

PREDICTED DIALYSIS COST OF APPROXIMATELY $ 11 TRILLION$ 11 TRILLION FOR THE COMING DECADE

400

200

Lysaght MJ J Am Soc Nephrol 2002 13 S37-40

De Vecchi AF et al NDT 1999

Dialysis Cost Europe

25 - 38 times gt National Average

Prevalence of ESRD in 2004 versus economic welfare in the 75 Prevalence of ESRD in 2004 versus economic welfare in the 75 countries with the largest ESRD patient populationscountries with the largest ESRD patient populations

Grassmann A et al Nephrol Dial Transplant 2005 202587-2593

Regional ESRD distributionRegion Pop GDP ESRD

million US$ (000) Prevalence pmp

EU 380 217 790Europe 804 120 393M East 271 32 150Africa 833 10 55LAmerica 512 38 310Asia 3316 11 55Japan 127 376 1830NAmerica 310 295 1400

Moeller S et al Nephrol Dial Transplant 2002 Dec17(12)2071-6

Morelinkage

withGDP

than the general

population

China Future Dialysis Expense

￥0

￥5

￥10

￥15

￥20

￥25

￥30

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Bill

ions

Ann

ual E

xpen

ditu

re o

n D

ialy

sis

￥7143670260

￥29087632671Factors98 dialysis population growth per yearModality share remains 90 HD 10 PD

Source amp Courtesy CMIA 2006 data

(From 71 billion in 2005 to 29 billion in 2020)

TIME December 8 2003Newsweek Sept 4 2000

Percentage of incident patients

with diabetes 2006

data presented only for those countries from which relevant information was available All rates are unadjusted ^UK England Wales amp Northern Ireland (Scotland data reported separately) Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only Latest data for Canada Croatia amp Italy are for 2005 Data for France include 13 regions in 2005 amp 15 regions in 2006

1 Malaysia 5752 Mexico 4993 USA 4434 Japan 4255 Taiwan 424

8 Hong Kong 41

18 Australia 324

USRDS 2008

Diagnosis Distribution of NEW patients 2006 - 2007GN

217

Obstructive28

Unknown179

DM393

Others38

HTvascular106

Inherited cong30

Infection reflux08

新症病人之病因 (2006-7)

感染

遺傳

尿道阻塞

高血壓糖尿病

腎小球腎炎

DM 393

GN 217

Hong Kong Renal Registry香港醫院管理局腎病註冊

World

20002030

154 m370 m

55 m84 m

Developed Developing

99 m286 m

167338

329

182

524307

28391

809

228

423

186

09 16

20002030

In million subjects

102

81

71

211

255

127

78

THE GLOBAL BURDEN OF DIABETES (2000-2030)

WHO March 2003

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Consensus Workshop

Part 1 Detection of chronic kidney disease

Part 2 Evaluation and estimating progression of chronic kidney disease

Part 3 Measures to prevent the progression of chronic kidney disease

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)s2-7

Summary of the Consensus Statements (1)Summary of the Consensus Statements (1)

bull It is recommended to establish a global surveillance center (ISN Kidney Disease Data Centre or ISN KDDC) to coordinate worldwide standardized screening studies with standardized screening techniques in appropriate target groups to allow for the collection of clearly comparable data

bull It is recommended that patients diagnosed with diabetes and hypertension

should have regular screening for development of kidney disease

bull It is recommended that close relatives of patients with nephropathy due to diabetes hypertension and glomerulonephritis should also be the primary targets for screening to detect clinically silent kidney disease

bull No consensus was made on an exact age ldquocut-offrdquo for initiating CKD screening

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

SHAREScreening for Hong Kong Asymptomatic Renal

Population and Evaluation programme

普查計劃

腎康體健

Li PKT et al Kidney Int 2005 Apr(94)s36-40

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

325

585

90

Injuries(51 million)

Noncommunicableconditions(331 million)

WORLDDeaths by broad cause group 2001

Communicable diseases maternal and perinatal

conditions and nutritional deficiencies

(184 million)

Total deaths 56554000

Source World Health Report 2002

Yach D et al JAMA 20042912616-2622

Global Mortality From Chronic DiseasesGlobal Mortality From Chronic DiseasesChronic diseases Injuries and

Communicable diseases

In 2002 the leading chronic diseases caused 29 million deaths worldwide

Yach D et al JAMA 20042912616-2622

Global Mortality From Chronic DiseasesGlobal Mortality From Chronic DiseasesChronic diseases Injuries and

Communicable diseases

In 2002 the leading chronic diseases caused 29 million deaths worldwide

CVS

Neoplasm

OthersCOADDM

Projections of Global Mortality and BurdenProjections of Global Mortality and Burdenof Disease from 2002 to 2030of Disease from 2002 to 2030

Changes in Rankings for 15 Leading Causes of Death 2002 and 2030

Colin D Mathers Dejan LoncarEvidence and Information for Policy Cluster World Health Organization Geneva Switzerland

Mathers CD Loncar D PLoS Med 2006 Nov3(11)e442

GLOBAL MAINTENANCE DIALYSIS POPULATION FROM 1990 TO 2010

1990 2000 2010

426000

1490000

2500000

Lysaght MJ J Am Soc Nephrol 2002 13 S37-40

Incidence of ESRD 2006

Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only

USRDS 2008

1 Taiwan 4182 USA 3633 Mexico 3464 Shanghai 2825 Japan 275

22 HK 140

30 NZ 11531 Australia 115

Prevalence of ESRD 2006

Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only

1 Taiwan 22262 Japan 19563 USA 16414 Germany 1114

7 HK 994

18 NZ 77819 Australia778

USRDS 2008

Age-specific prevalence of CKD (per 100 individuals) from 1996 to 2003 and incidence (per 100 person-years) from 1997 to 2003

Kuo HW et al Am J Kidney Dis 2007 Jan49(1)46-55 Prev

alen

ce (p

er 1

00 in

divi

dual

s) I

ncid

ence

(per

100

per

son-

year

s)

Year

Incidence

75+

65-74

45-64

20-44

0-19

Odds Ratio of 1395 for ge75 years compared with lt 20 years

Epidemiological features of CKD in Taiwan Epidemiological features of CKD in Taiwan bull 200000 individuals randomly sampled from 1996 to 2003

bull The prevalence CKD increased from 199 in 1996 to 983 in 2003

bull The overall incidence rate during 1997 to 2003 was 135100 person-years

bull Age is a key predictor of CKD ndash Odds Ratio of 1395 for age ge75 years compared with age lt 20

years

bull Other risk factors of CKD ndash diabetes ndash hypertension ndash hyperlipidemiandash female sex

Kuo HW et al Am J Kidney Dis 2007 Jan49(1)46-55

NEOERICA dataNHANES data

00402lt 15 (or on dialysis)

5020215 ndash 294464330 ndash 593

3060 ndash 892

33ge 901

UK Prevalence ()

US PopulationPrevalence ()

GFR mlmin173 m2

CKDStage

Coresh J et al Am J Kidney Dis 2003 41 1-12De Lusignan S et al Fam Pract 2005 22 234-41

Lifetime cumulative risks for ESRD Lifetime cumulative risks for ESRD

Kiberd B J Am Soc Nephrol 2006 Nov17(11)2967-73

8 for black women

3 for white men

78 for black men

22 for white women

CHINA ESRD StatusCHINA ESRD Status

bull About 75000 ESRD patients in Mainland China are receiving treatment today

bull Nearly 2 million patients may be untreated

bull The rate of growth of treated ESRD patients is 10-12 per year

bull ESRD treatments are high cost

Presented in ISPD 2006 Asia Round table on Dialysis Economics from CMIA(Chinese Medical Insurance Agency)

China ESRD Growth Rate To Exceed That of Population

1150000000

1200000000

1250000000

1300000000

1350000000

1400000000

1450000000

1500000000

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Tota

l Pop

ulat

ion

0

50000

100000

150000

200000

250000

300000

350000

ESR

D P

atie

nts

Population Dialysis patients

ACTUAL PROJECTED

ESRD Patients07 per year

~10-12 per year

Population

Source amp CourtesyCMIA 2006 data

Incidence of ESRF (for 12 months ending 31032007) 1074 (164 pmp)

641697

789 798 830885

1019 1012960

1045 1040 1074

0100200300400500600700800900

100011001200

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

Incidence of ESRF on RRT

Hong Kong Renal Registry香港醫院管理局腎病註冊

Incidence of ESRD (pmp) by age 2005

USRDS 2007

0-19 20-44 45-64 65-74 gt75

No14 No 4 No 5 No 8 No 24

(Japan - no data)

No of patient on renal replacement therapy 7160 ( 1025 pmp)

Hong Kong Renal Registry香港醫院管理局腎病註冊1998rarr2008 uarr 19 times

The reasons of this growth are

ndash Global ageing

ndash Multi-morbid population

ndash Higher life-expectancy of ESRD patients

ndash Increasing access of younger people in countries in which RRT has been limited until today

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Lung Cancer

KidneyFailure

ColonCancer

BreastCancer

Prostate Cancer

57

99

4232

Kidney Failure Compared to Cancer Deaths in the US in 2000

(in Thousands)157

SEER 2003(Surveillance Epidemiology and End Results)

1200

600

0

Ten

year

med

ical

cos

ts o

f di

alys

is p

opul

atio

n$

( bill

ions

)

1981-1990 1991-2000 2001-2010

800

1000

$

$

$

PREDICTED DIALYSIS COST OF APPROXIMATELY $ 11 TRILLION$ 11 TRILLION FOR THE COMING DECADE

400

200

Lysaght MJ J Am Soc Nephrol 2002 13 S37-40

De Vecchi AF et al NDT 1999

Dialysis Cost Europe

25 - 38 times gt National Average

Prevalence of ESRD in 2004 versus economic welfare in the 75 Prevalence of ESRD in 2004 versus economic welfare in the 75 countries with the largest ESRD patient populationscountries with the largest ESRD patient populations

Grassmann A et al Nephrol Dial Transplant 2005 202587-2593

Regional ESRD distributionRegion Pop GDP ESRD

million US$ (000) Prevalence pmp

EU 380 217 790Europe 804 120 393M East 271 32 150Africa 833 10 55LAmerica 512 38 310Asia 3316 11 55Japan 127 376 1830NAmerica 310 295 1400

Moeller S et al Nephrol Dial Transplant 2002 Dec17(12)2071-6

Morelinkage

withGDP

than the general

population

China Future Dialysis Expense

￥0

￥5

￥10

￥15

￥20

￥25

￥30

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Bill

ions

Ann

ual E

xpen

ditu

re o

n D

ialy

sis

￥7143670260

￥29087632671Factors98 dialysis population growth per yearModality share remains 90 HD 10 PD

Source amp Courtesy CMIA 2006 data

(From 71 billion in 2005 to 29 billion in 2020)

TIME December 8 2003Newsweek Sept 4 2000

Percentage of incident patients

with diabetes 2006

data presented only for those countries from which relevant information was available All rates are unadjusted ^UK England Wales amp Northern Ireland (Scotland data reported separately) Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only Latest data for Canada Croatia amp Italy are for 2005 Data for France include 13 regions in 2005 amp 15 regions in 2006

1 Malaysia 5752 Mexico 4993 USA 4434 Japan 4255 Taiwan 424

8 Hong Kong 41

18 Australia 324

USRDS 2008

Diagnosis Distribution of NEW patients 2006 - 2007GN

217

Obstructive28

Unknown179

DM393

Others38

HTvascular106

Inherited cong30

Infection reflux08

新症病人之病因 (2006-7)

感染

遺傳

尿道阻塞

高血壓糖尿病

腎小球腎炎

DM 393

GN 217

Hong Kong Renal Registry香港醫院管理局腎病註冊

World

20002030

154 m370 m

55 m84 m

Developed Developing

99 m286 m

167338

329

182

524307

28391

809

228

423

186

09 16

20002030

In million subjects

102

81

71

211

255

127

78

THE GLOBAL BURDEN OF DIABETES (2000-2030)

WHO March 2003

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Consensus Workshop

Part 1 Detection of chronic kidney disease

Part 2 Evaluation and estimating progression of chronic kidney disease

Part 3 Measures to prevent the progression of chronic kidney disease

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)s2-7

Summary of the Consensus Statements (1)Summary of the Consensus Statements (1)

bull It is recommended to establish a global surveillance center (ISN Kidney Disease Data Centre or ISN KDDC) to coordinate worldwide standardized screening studies with standardized screening techniques in appropriate target groups to allow for the collection of clearly comparable data

bull It is recommended that patients diagnosed with diabetes and hypertension

should have regular screening for development of kidney disease

bull It is recommended that close relatives of patients with nephropathy due to diabetes hypertension and glomerulonephritis should also be the primary targets for screening to detect clinically silent kidney disease

bull No consensus was made on an exact age ldquocut-offrdquo for initiating CKD screening

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

SHAREScreening for Hong Kong Asymptomatic Renal

Population and Evaluation programme

普查計劃

腎康體健

Li PKT et al Kidney Int 2005 Apr(94)s36-40

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Yach D et al JAMA 20042912616-2622

Global Mortality From Chronic DiseasesGlobal Mortality From Chronic DiseasesChronic diseases Injuries and

Communicable diseases

In 2002 the leading chronic diseases caused 29 million deaths worldwide

Yach D et al JAMA 20042912616-2622

Global Mortality From Chronic DiseasesGlobal Mortality From Chronic DiseasesChronic diseases Injuries and

Communicable diseases

In 2002 the leading chronic diseases caused 29 million deaths worldwide

CVS

Neoplasm

OthersCOADDM

Projections of Global Mortality and BurdenProjections of Global Mortality and Burdenof Disease from 2002 to 2030of Disease from 2002 to 2030

Changes in Rankings for 15 Leading Causes of Death 2002 and 2030

Colin D Mathers Dejan LoncarEvidence and Information for Policy Cluster World Health Organization Geneva Switzerland

Mathers CD Loncar D PLoS Med 2006 Nov3(11)e442

GLOBAL MAINTENANCE DIALYSIS POPULATION FROM 1990 TO 2010

1990 2000 2010

426000

1490000

2500000

Lysaght MJ J Am Soc Nephrol 2002 13 S37-40

Incidence of ESRD 2006

Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only

USRDS 2008

1 Taiwan 4182 USA 3633 Mexico 3464 Shanghai 2825 Japan 275

22 HK 140

30 NZ 11531 Australia 115

Prevalence of ESRD 2006

Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only

1 Taiwan 22262 Japan 19563 USA 16414 Germany 1114

7 HK 994

18 NZ 77819 Australia778

USRDS 2008

Age-specific prevalence of CKD (per 100 individuals) from 1996 to 2003 and incidence (per 100 person-years) from 1997 to 2003

Kuo HW et al Am J Kidney Dis 2007 Jan49(1)46-55 Prev

alen

ce (p

er 1

00 in

divi

dual

s) I

ncid

ence

(per

100

per

son-

year

s)

Year

Incidence

75+

65-74

45-64

20-44

0-19

Odds Ratio of 1395 for ge75 years compared with lt 20 years

Epidemiological features of CKD in Taiwan Epidemiological features of CKD in Taiwan bull 200000 individuals randomly sampled from 1996 to 2003

bull The prevalence CKD increased from 199 in 1996 to 983 in 2003

bull The overall incidence rate during 1997 to 2003 was 135100 person-years

bull Age is a key predictor of CKD ndash Odds Ratio of 1395 for age ge75 years compared with age lt 20

years

bull Other risk factors of CKD ndash diabetes ndash hypertension ndash hyperlipidemiandash female sex

Kuo HW et al Am J Kidney Dis 2007 Jan49(1)46-55

NEOERICA dataNHANES data

00402lt 15 (or on dialysis)

5020215 ndash 294464330 ndash 593

3060 ndash 892

33ge 901

UK Prevalence ()

US PopulationPrevalence ()

GFR mlmin173 m2

CKDStage

Coresh J et al Am J Kidney Dis 2003 41 1-12De Lusignan S et al Fam Pract 2005 22 234-41

Lifetime cumulative risks for ESRD Lifetime cumulative risks for ESRD

Kiberd B J Am Soc Nephrol 2006 Nov17(11)2967-73

8 for black women

3 for white men

78 for black men

22 for white women

CHINA ESRD StatusCHINA ESRD Status

bull About 75000 ESRD patients in Mainland China are receiving treatment today

bull Nearly 2 million patients may be untreated

bull The rate of growth of treated ESRD patients is 10-12 per year

bull ESRD treatments are high cost

Presented in ISPD 2006 Asia Round table on Dialysis Economics from CMIA(Chinese Medical Insurance Agency)

China ESRD Growth Rate To Exceed That of Population

1150000000

1200000000

1250000000

1300000000

1350000000

1400000000

1450000000

1500000000

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Tota

l Pop

ulat

ion

0

50000

100000

150000

200000

250000

300000

350000

ESR

D P

atie

nts

Population Dialysis patients

ACTUAL PROJECTED

ESRD Patients07 per year

~10-12 per year

Population

Source amp CourtesyCMIA 2006 data

Incidence of ESRF (for 12 months ending 31032007) 1074 (164 pmp)

641697

789 798 830885

1019 1012960

1045 1040 1074

0100200300400500600700800900

100011001200

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

Incidence of ESRF on RRT

Hong Kong Renal Registry香港醫院管理局腎病註冊

Incidence of ESRD (pmp) by age 2005

USRDS 2007

0-19 20-44 45-64 65-74 gt75

No14 No 4 No 5 No 8 No 24

(Japan - no data)

No of patient on renal replacement therapy 7160 ( 1025 pmp)

Hong Kong Renal Registry香港醫院管理局腎病註冊1998rarr2008 uarr 19 times

The reasons of this growth are

ndash Global ageing

ndash Multi-morbid population

ndash Higher life-expectancy of ESRD patients

ndash Increasing access of younger people in countries in which RRT has been limited until today

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Lung Cancer

KidneyFailure

ColonCancer

BreastCancer

Prostate Cancer

57

99

4232

Kidney Failure Compared to Cancer Deaths in the US in 2000

(in Thousands)157

SEER 2003(Surveillance Epidemiology and End Results)

1200

600

0

Ten

year

med

ical

cos

ts o

f di

alys

is p

opul

atio

n$

( bill

ions

)

1981-1990 1991-2000 2001-2010

800

1000

$

$

$

PREDICTED DIALYSIS COST OF APPROXIMATELY $ 11 TRILLION$ 11 TRILLION FOR THE COMING DECADE

400

200

Lysaght MJ J Am Soc Nephrol 2002 13 S37-40

De Vecchi AF et al NDT 1999

Dialysis Cost Europe

25 - 38 times gt National Average

Prevalence of ESRD in 2004 versus economic welfare in the 75 Prevalence of ESRD in 2004 versus economic welfare in the 75 countries with the largest ESRD patient populationscountries with the largest ESRD patient populations

Grassmann A et al Nephrol Dial Transplant 2005 202587-2593

Regional ESRD distributionRegion Pop GDP ESRD

million US$ (000) Prevalence pmp

EU 380 217 790Europe 804 120 393M East 271 32 150Africa 833 10 55LAmerica 512 38 310Asia 3316 11 55Japan 127 376 1830NAmerica 310 295 1400

Moeller S et al Nephrol Dial Transplant 2002 Dec17(12)2071-6

Morelinkage

withGDP

than the general

population

China Future Dialysis Expense

￥0

￥5

￥10

￥15

￥20

￥25

￥30

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Bill

ions

Ann

ual E

xpen

ditu

re o

n D

ialy

sis

￥7143670260

￥29087632671Factors98 dialysis population growth per yearModality share remains 90 HD 10 PD

Source amp Courtesy CMIA 2006 data

(From 71 billion in 2005 to 29 billion in 2020)

TIME December 8 2003Newsweek Sept 4 2000

Percentage of incident patients

with diabetes 2006

data presented only for those countries from which relevant information was available All rates are unadjusted ^UK England Wales amp Northern Ireland (Scotland data reported separately) Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only Latest data for Canada Croatia amp Italy are for 2005 Data for France include 13 regions in 2005 amp 15 regions in 2006

1 Malaysia 5752 Mexico 4993 USA 4434 Japan 4255 Taiwan 424

8 Hong Kong 41

18 Australia 324

USRDS 2008

Diagnosis Distribution of NEW patients 2006 - 2007GN

217

Obstructive28

Unknown179

DM393

Others38

HTvascular106

Inherited cong30

Infection reflux08

新症病人之病因 (2006-7)

感染

遺傳

尿道阻塞

高血壓糖尿病

腎小球腎炎

DM 393

GN 217

Hong Kong Renal Registry香港醫院管理局腎病註冊

World

20002030

154 m370 m

55 m84 m

Developed Developing

99 m286 m

167338

329

182

524307

28391

809

228

423

186

09 16

20002030

In million subjects

102

81

71

211

255

127

78

THE GLOBAL BURDEN OF DIABETES (2000-2030)

WHO March 2003

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Consensus Workshop

Part 1 Detection of chronic kidney disease

Part 2 Evaluation and estimating progression of chronic kidney disease

Part 3 Measures to prevent the progression of chronic kidney disease

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)s2-7

Summary of the Consensus Statements (1)Summary of the Consensus Statements (1)

bull It is recommended to establish a global surveillance center (ISN Kidney Disease Data Centre or ISN KDDC) to coordinate worldwide standardized screening studies with standardized screening techniques in appropriate target groups to allow for the collection of clearly comparable data

bull It is recommended that patients diagnosed with diabetes and hypertension

should have regular screening for development of kidney disease

bull It is recommended that close relatives of patients with nephropathy due to diabetes hypertension and glomerulonephritis should also be the primary targets for screening to detect clinically silent kidney disease

bull No consensus was made on an exact age ldquocut-offrdquo for initiating CKD screening

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

SHAREScreening for Hong Kong Asymptomatic Renal

Population and Evaluation programme

普查計劃

腎康體健

Li PKT et al Kidney Int 2005 Apr(94)s36-40

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Yach D et al JAMA 20042912616-2622

Global Mortality From Chronic DiseasesGlobal Mortality From Chronic DiseasesChronic diseases Injuries and

Communicable diseases

In 2002 the leading chronic diseases caused 29 million deaths worldwide

CVS

Neoplasm

OthersCOADDM

Projections of Global Mortality and BurdenProjections of Global Mortality and Burdenof Disease from 2002 to 2030of Disease from 2002 to 2030

Changes in Rankings for 15 Leading Causes of Death 2002 and 2030

Colin D Mathers Dejan LoncarEvidence and Information for Policy Cluster World Health Organization Geneva Switzerland

Mathers CD Loncar D PLoS Med 2006 Nov3(11)e442

GLOBAL MAINTENANCE DIALYSIS POPULATION FROM 1990 TO 2010

1990 2000 2010

426000

1490000

2500000

Lysaght MJ J Am Soc Nephrol 2002 13 S37-40

Incidence of ESRD 2006

Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only

USRDS 2008

1 Taiwan 4182 USA 3633 Mexico 3464 Shanghai 2825 Japan 275

22 HK 140

30 NZ 11531 Australia 115

Prevalence of ESRD 2006

Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only

1 Taiwan 22262 Japan 19563 USA 16414 Germany 1114

7 HK 994

18 NZ 77819 Australia778

USRDS 2008

Age-specific prevalence of CKD (per 100 individuals) from 1996 to 2003 and incidence (per 100 person-years) from 1997 to 2003

Kuo HW et al Am J Kidney Dis 2007 Jan49(1)46-55 Prev

alen

ce (p

er 1

00 in

divi

dual

s) I

ncid

ence

(per

100

per

son-

year

s)

Year

Incidence

75+

65-74

45-64

20-44

0-19

Odds Ratio of 1395 for ge75 years compared with lt 20 years

Epidemiological features of CKD in Taiwan Epidemiological features of CKD in Taiwan bull 200000 individuals randomly sampled from 1996 to 2003

bull The prevalence CKD increased from 199 in 1996 to 983 in 2003

bull The overall incidence rate during 1997 to 2003 was 135100 person-years

bull Age is a key predictor of CKD ndash Odds Ratio of 1395 for age ge75 years compared with age lt 20

years

bull Other risk factors of CKD ndash diabetes ndash hypertension ndash hyperlipidemiandash female sex

Kuo HW et al Am J Kidney Dis 2007 Jan49(1)46-55

NEOERICA dataNHANES data

00402lt 15 (or on dialysis)

5020215 ndash 294464330 ndash 593

3060 ndash 892

33ge 901

UK Prevalence ()

US PopulationPrevalence ()

GFR mlmin173 m2

CKDStage

Coresh J et al Am J Kidney Dis 2003 41 1-12De Lusignan S et al Fam Pract 2005 22 234-41

Lifetime cumulative risks for ESRD Lifetime cumulative risks for ESRD

Kiberd B J Am Soc Nephrol 2006 Nov17(11)2967-73

8 for black women

3 for white men

78 for black men

22 for white women

CHINA ESRD StatusCHINA ESRD Status

bull About 75000 ESRD patients in Mainland China are receiving treatment today

bull Nearly 2 million patients may be untreated

bull The rate of growth of treated ESRD patients is 10-12 per year

bull ESRD treatments are high cost

Presented in ISPD 2006 Asia Round table on Dialysis Economics from CMIA(Chinese Medical Insurance Agency)

China ESRD Growth Rate To Exceed That of Population

1150000000

1200000000

1250000000

1300000000

1350000000

1400000000

1450000000

1500000000

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Tota

l Pop

ulat

ion

0

50000

100000

150000

200000

250000

300000

350000

ESR

D P

atie

nts

Population Dialysis patients

ACTUAL PROJECTED

ESRD Patients07 per year

~10-12 per year

Population

Source amp CourtesyCMIA 2006 data

Incidence of ESRF (for 12 months ending 31032007) 1074 (164 pmp)

641697

789 798 830885

1019 1012960

1045 1040 1074

0100200300400500600700800900

100011001200

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

Incidence of ESRF on RRT

Hong Kong Renal Registry香港醫院管理局腎病註冊

Incidence of ESRD (pmp) by age 2005

USRDS 2007

0-19 20-44 45-64 65-74 gt75

No14 No 4 No 5 No 8 No 24

(Japan - no data)

No of patient on renal replacement therapy 7160 ( 1025 pmp)

Hong Kong Renal Registry香港醫院管理局腎病註冊1998rarr2008 uarr 19 times

The reasons of this growth are

ndash Global ageing

ndash Multi-morbid population

ndash Higher life-expectancy of ESRD patients

ndash Increasing access of younger people in countries in which RRT has been limited until today

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Lung Cancer

KidneyFailure

ColonCancer

BreastCancer

Prostate Cancer

57

99

4232

Kidney Failure Compared to Cancer Deaths in the US in 2000

(in Thousands)157

SEER 2003(Surveillance Epidemiology and End Results)

1200

600

0

Ten

year

med

ical

cos

ts o

f di

alys

is p

opul

atio

n$

( bill

ions

)

1981-1990 1991-2000 2001-2010

800

1000

$

$

$

PREDICTED DIALYSIS COST OF APPROXIMATELY $ 11 TRILLION$ 11 TRILLION FOR THE COMING DECADE

400

200

Lysaght MJ J Am Soc Nephrol 2002 13 S37-40

De Vecchi AF et al NDT 1999

Dialysis Cost Europe

25 - 38 times gt National Average

Prevalence of ESRD in 2004 versus economic welfare in the 75 Prevalence of ESRD in 2004 versus economic welfare in the 75 countries with the largest ESRD patient populationscountries with the largest ESRD patient populations

Grassmann A et al Nephrol Dial Transplant 2005 202587-2593

Regional ESRD distributionRegion Pop GDP ESRD

million US$ (000) Prevalence pmp

EU 380 217 790Europe 804 120 393M East 271 32 150Africa 833 10 55LAmerica 512 38 310Asia 3316 11 55Japan 127 376 1830NAmerica 310 295 1400

Moeller S et al Nephrol Dial Transplant 2002 Dec17(12)2071-6

Morelinkage

withGDP

than the general

population

China Future Dialysis Expense

￥0

￥5

￥10

￥15

￥20

￥25

￥30

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Bill

ions

Ann

ual E

xpen

ditu

re o

n D

ialy

sis

￥7143670260

￥29087632671Factors98 dialysis population growth per yearModality share remains 90 HD 10 PD

Source amp Courtesy CMIA 2006 data

(From 71 billion in 2005 to 29 billion in 2020)

TIME December 8 2003Newsweek Sept 4 2000

Percentage of incident patients

with diabetes 2006

data presented only for those countries from which relevant information was available All rates are unadjusted ^UK England Wales amp Northern Ireland (Scotland data reported separately) Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only Latest data for Canada Croatia amp Italy are for 2005 Data for France include 13 regions in 2005 amp 15 regions in 2006

1 Malaysia 5752 Mexico 4993 USA 4434 Japan 4255 Taiwan 424

8 Hong Kong 41

18 Australia 324

USRDS 2008

Diagnosis Distribution of NEW patients 2006 - 2007GN

217

Obstructive28

Unknown179

DM393

Others38

HTvascular106

Inherited cong30

Infection reflux08

新症病人之病因 (2006-7)

感染

遺傳

尿道阻塞

高血壓糖尿病

腎小球腎炎

DM 393

GN 217

Hong Kong Renal Registry香港醫院管理局腎病註冊

World

20002030

154 m370 m

55 m84 m

Developed Developing

99 m286 m

167338

329

182

524307

28391

809

228

423

186

09 16

20002030

In million subjects

102

81

71

211

255

127

78

THE GLOBAL BURDEN OF DIABETES (2000-2030)

WHO March 2003

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Consensus Workshop

Part 1 Detection of chronic kidney disease

Part 2 Evaluation and estimating progression of chronic kidney disease

Part 3 Measures to prevent the progression of chronic kidney disease

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)s2-7

Summary of the Consensus Statements (1)Summary of the Consensus Statements (1)

bull It is recommended to establish a global surveillance center (ISN Kidney Disease Data Centre or ISN KDDC) to coordinate worldwide standardized screening studies with standardized screening techniques in appropriate target groups to allow for the collection of clearly comparable data

bull It is recommended that patients diagnosed with diabetes and hypertension

should have regular screening for development of kidney disease

bull It is recommended that close relatives of patients with nephropathy due to diabetes hypertension and glomerulonephritis should also be the primary targets for screening to detect clinically silent kidney disease

bull No consensus was made on an exact age ldquocut-offrdquo for initiating CKD screening

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

SHAREScreening for Hong Kong Asymptomatic Renal

Population and Evaluation programme

普查計劃

腎康體健

Li PKT et al Kidney Int 2005 Apr(94)s36-40

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Projections of Global Mortality and BurdenProjections of Global Mortality and Burdenof Disease from 2002 to 2030of Disease from 2002 to 2030

Changes in Rankings for 15 Leading Causes of Death 2002 and 2030

Colin D Mathers Dejan LoncarEvidence and Information for Policy Cluster World Health Organization Geneva Switzerland

Mathers CD Loncar D PLoS Med 2006 Nov3(11)e442

GLOBAL MAINTENANCE DIALYSIS POPULATION FROM 1990 TO 2010

1990 2000 2010

426000

1490000

2500000

Lysaght MJ J Am Soc Nephrol 2002 13 S37-40

Incidence of ESRD 2006

Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only

USRDS 2008

1 Taiwan 4182 USA 3633 Mexico 3464 Shanghai 2825 Japan 275

22 HK 140

30 NZ 11531 Australia 115

Prevalence of ESRD 2006

Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only

1 Taiwan 22262 Japan 19563 USA 16414 Germany 1114

7 HK 994

18 NZ 77819 Australia778

USRDS 2008

Age-specific prevalence of CKD (per 100 individuals) from 1996 to 2003 and incidence (per 100 person-years) from 1997 to 2003

Kuo HW et al Am J Kidney Dis 2007 Jan49(1)46-55 Prev

alen

ce (p

er 1

00 in

divi

dual

s) I

ncid

ence

(per

100

per

son-

year

s)

Year

Incidence

75+

65-74

45-64

20-44

0-19

Odds Ratio of 1395 for ge75 years compared with lt 20 years

Epidemiological features of CKD in Taiwan Epidemiological features of CKD in Taiwan bull 200000 individuals randomly sampled from 1996 to 2003

bull The prevalence CKD increased from 199 in 1996 to 983 in 2003

bull The overall incidence rate during 1997 to 2003 was 135100 person-years

bull Age is a key predictor of CKD ndash Odds Ratio of 1395 for age ge75 years compared with age lt 20

years

bull Other risk factors of CKD ndash diabetes ndash hypertension ndash hyperlipidemiandash female sex

Kuo HW et al Am J Kidney Dis 2007 Jan49(1)46-55

NEOERICA dataNHANES data

00402lt 15 (or on dialysis)

5020215 ndash 294464330 ndash 593

3060 ndash 892

33ge 901

UK Prevalence ()

US PopulationPrevalence ()

GFR mlmin173 m2

CKDStage

Coresh J et al Am J Kidney Dis 2003 41 1-12De Lusignan S et al Fam Pract 2005 22 234-41

Lifetime cumulative risks for ESRD Lifetime cumulative risks for ESRD

Kiberd B J Am Soc Nephrol 2006 Nov17(11)2967-73

8 for black women

3 for white men

78 for black men

22 for white women

CHINA ESRD StatusCHINA ESRD Status

bull About 75000 ESRD patients in Mainland China are receiving treatment today

bull Nearly 2 million patients may be untreated

bull The rate of growth of treated ESRD patients is 10-12 per year

bull ESRD treatments are high cost

Presented in ISPD 2006 Asia Round table on Dialysis Economics from CMIA(Chinese Medical Insurance Agency)

China ESRD Growth Rate To Exceed That of Population

1150000000

1200000000

1250000000

1300000000

1350000000

1400000000

1450000000

1500000000

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Tota

l Pop

ulat

ion

0

50000

100000

150000

200000

250000

300000

350000

ESR

D P

atie

nts

Population Dialysis patients

ACTUAL PROJECTED

ESRD Patients07 per year

~10-12 per year

Population

Source amp CourtesyCMIA 2006 data

Incidence of ESRF (for 12 months ending 31032007) 1074 (164 pmp)

641697

789 798 830885

1019 1012960

1045 1040 1074

0100200300400500600700800900

100011001200

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

Incidence of ESRF on RRT

Hong Kong Renal Registry香港醫院管理局腎病註冊

Incidence of ESRD (pmp) by age 2005

USRDS 2007

0-19 20-44 45-64 65-74 gt75

No14 No 4 No 5 No 8 No 24

(Japan - no data)

No of patient on renal replacement therapy 7160 ( 1025 pmp)

Hong Kong Renal Registry香港醫院管理局腎病註冊1998rarr2008 uarr 19 times

The reasons of this growth are

ndash Global ageing

ndash Multi-morbid population

ndash Higher life-expectancy of ESRD patients

ndash Increasing access of younger people in countries in which RRT has been limited until today

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Lung Cancer

KidneyFailure

ColonCancer

BreastCancer

Prostate Cancer

57

99

4232

Kidney Failure Compared to Cancer Deaths in the US in 2000

(in Thousands)157

SEER 2003(Surveillance Epidemiology and End Results)

1200

600

0

Ten

year

med

ical

cos

ts o

f di

alys

is p

opul

atio

n$

( bill

ions

)

1981-1990 1991-2000 2001-2010

800

1000

$

$

$

PREDICTED DIALYSIS COST OF APPROXIMATELY $ 11 TRILLION$ 11 TRILLION FOR THE COMING DECADE

400

200

Lysaght MJ J Am Soc Nephrol 2002 13 S37-40

De Vecchi AF et al NDT 1999

Dialysis Cost Europe

25 - 38 times gt National Average

Prevalence of ESRD in 2004 versus economic welfare in the 75 Prevalence of ESRD in 2004 versus economic welfare in the 75 countries with the largest ESRD patient populationscountries with the largest ESRD patient populations

Grassmann A et al Nephrol Dial Transplant 2005 202587-2593

Regional ESRD distributionRegion Pop GDP ESRD

million US$ (000) Prevalence pmp

EU 380 217 790Europe 804 120 393M East 271 32 150Africa 833 10 55LAmerica 512 38 310Asia 3316 11 55Japan 127 376 1830NAmerica 310 295 1400

Moeller S et al Nephrol Dial Transplant 2002 Dec17(12)2071-6

Morelinkage

withGDP

than the general

population

China Future Dialysis Expense

￥0

￥5

￥10

￥15

￥20

￥25

￥30

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Bill

ions

Ann

ual E

xpen

ditu

re o

n D

ialy

sis

￥7143670260

￥29087632671Factors98 dialysis population growth per yearModality share remains 90 HD 10 PD

Source amp Courtesy CMIA 2006 data

(From 71 billion in 2005 to 29 billion in 2020)

TIME December 8 2003Newsweek Sept 4 2000

Percentage of incident patients

with diabetes 2006

data presented only for those countries from which relevant information was available All rates are unadjusted ^UK England Wales amp Northern Ireland (Scotland data reported separately) Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only Latest data for Canada Croatia amp Italy are for 2005 Data for France include 13 regions in 2005 amp 15 regions in 2006

1 Malaysia 5752 Mexico 4993 USA 4434 Japan 4255 Taiwan 424

8 Hong Kong 41

18 Australia 324

USRDS 2008

Diagnosis Distribution of NEW patients 2006 - 2007GN

217

Obstructive28

Unknown179

DM393

Others38

HTvascular106

Inherited cong30

Infection reflux08

新症病人之病因 (2006-7)

感染

遺傳

尿道阻塞

高血壓糖尿病

腎小球腎炎

DM 393

GN 217

Hong Kong Renal Registry香港醫院管理局腎病註冊

World

20002030

154 m370 m

55 m84 m

Developed Developing

99 m286 m

167338

329

182

524307

28391

809

228

423

186

09 16

20002030

In million subjects

102

81

71

211

255

127

78

THE GLOBAL BURDEN OF DIABETES (2000-2030)

WHO March 2003

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Consensus Workshop

Part 1 Detection of chronic kidney disease

Part 2 Evaluation and estimating progression of chronic kidney disease

Part 3 Measures to prevent the progression of chronic kidney disease

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)s2-7

Summary of the Consensus Statements (1)Summary of the Consensus Statements (1)

bull It is recommended to establish a global surveillance center (ISN Kidney Disease Data Centre or ISN KDDC) to coordinate worldwide standardized screening studies with standardized screening techniques in appropriate target groups to allow for the collection of clearly comparable data

bull It is recommended that patients diagnosed with diabetes and hypertension

should have regular screening for development of kidney disease

bull It is recommended that close relatives of patients with nephropathy due to diabetes hypertension and glomerulonephritis should also be the primary targets for screening to detect clinically silent kidney disease

bull No consensus was made on an exact age ldquocut-offrdquo for initiating CKD screening

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

SHAREScreening for Hong Kong Asymptomatic Renal

Population and Evaluation programme

普查計劃

腎康體健

Li PKT et al Kidney Int 2005 Apr(94)s36-40

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

GLOBAL MAINTENANCE DIALYSIS POPULATION FROM 1990 TO 2010

1990 2000 2010

426000

1490000

2500000

Lysaght MJ J Am Soc Nephrol 2002 13 S37-40

Incidence of ESRD 2006

Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only

USRDS 2008

1 Taiwan 4182 USA 3633 Mexico 3464 Shanghai 2825 Japan 275

22 HK 140

30 NZ 11531 Australia 115

Prevalence of ESRD 2006

Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only

1 Taiwan 22262 Japan 19563 USA 16414 Germany 1114

7 HK 994

18 NZ 77819 Australia778

USRDS 2008

Age-specific prevalence of CKD (per 100 individuals) from 1996 to 2003 and incidence (per 100 person-years) from 1997 to 2003

Kuo HW et al Am J Kidney Dis 2007 Jan49(1)46-55 Prev

alen

ce (p

er 1

00 in

divi

dual

s) I

ncid

ence

(per

100

per

son-

year

s)

Year

Incidence

75+

65-74

45-64

20-44

0-19

Odds Ratio of 1395 for ge75 years compared with lt 20 years

Epidemiological features of CKD in Taiwan Epidemiological features of CKD in Taiwan bull 200000 individuals randomly sampled from 1996 to 2003

bull The prevalence CKD increased from 199 in 1996 to 983 in 2003

bull The overall incidence rate during 1997 to 2003 was 135100 person-years

bull Age is a key predictor of CKD ndash Odds Ratio of 1395 for age ge75 years compared with age lt 20

years

bull Other risk factors of CKD ndash diabetes ndash hypertension ndash hyperlipidemiandash female sex

Kuo HW et al Am J Kidney Dis 2007 Jan49(1)46-55

NEOERICA dataNHANES data

00402lt 15 (or on dialysis)

5020215 ndash 294464330 ndash 593

3060 ndash 892

33ge 901

UK Prevalence ()

US PopulationPrevalence ()

GFR mlmin173 m2

CKDStage

Coresh J et al Am J Kidney Dis 2003 41 1-12De Lusignan S et al Fam Pract 2005 22 234-41

Lifetime cumulative risks for ESRD Lifetime cumulative risks for ESRD

Kiberd B J Am Soc Nephrol 2006 Nov17(11)2967-73

8 for black women

3 for white men

78 for black men

22 for white women

CHINA ESRD StatusCHINA ESRD Status

bull About 75000 ESRD patients in Mainland China are receiving treatment today

bull Nearly 2 million patients may be untreated

bull The rate of growth of treated ESRD patients is 10-12 per year

bull ESRD treatments are high cost

Presented in ISPD 2006 Asia Round table on Dialysis Economics from CMIA(Chinese Medical Insurance Agency)

China ESRD Growth Rate To Exceed That of Population

1150000000

1200000000

1250000000

1300000000

1350000000

1400000000

1450000000

1500000000

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Tota

l Pop

ulat

ion

0

50000

100000

150000

200000

250000

300000

350000

ESR

D P

atie

nts

Population Dialysis patients

ACTUAL PROJECTED

ESRD Patients07 per year

~10-12 per year

Population

Source amp CourtesyCMIA 2006 data

Incidence of ESRF (for 12 months ending 31032007) 1074 (164 pmp)

641697

789 798 830885

1019 1012960

1045 1040 1074

0100200300400500600700800900

100011001200

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

Incidence of ESRF on RRT

Hong Kong Renal Registry香港醫院管理局腎病註冊

Incidence of ESRD (pmp) by age 2005

USRDS 2007

0-19 20-44 45-64 65-74 gt75

No14 No 4 No 5 No 8 No 24

(Japan - no data)

No of patient on renal replacement therapy 7160 ( 1025 pmp)

Hong Kong Renal Registry香港醫院管理局腎病註冊1998rarr2008 uarr 19 times

The reasons of this growth are

ndash Global ageing

ndash Multi-morbid population

ndash Higher life-expectancy of ESRD patients

ndash Increasing access of younger people in countries in which RRT has been limited until today

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Lung Cancer

KidneyFailure

ColonCancer

BreastCancer

Prostate Cancer

57

99

4232

Kidney Failure Compared to Cancer Deaths in the US in 2000

(in Thousands)157

SEER 2003(Surveillance Epidemiology and End Results)

1200

600

0

Ten

year

med

ical

cos

ts o

f di

alys

is p

opul

atio

n$

( bill

ions

)

1981-1990 1991-2000 2001-2010

800

1000

$

$

$

PREDICTED DIALYSIS COST OF APPROXIMATELY $ 11 TRILLION$ 11 TRILLION FOR THE COMING DECADE

400

200

Lysaght MJ J Am Soc Nephrol 2002 13 S37-40

De Vecchi AF et al NDT 1999

Dialysis Cost Europe

25 - 38 times gt National Average

Prevalence of ESRD in 2004 versus economic welfare in the 75 Prevalence of ESRD in 2004 versus economic welfare in the 75 countries with the largest ESRD patient populationscountries with the largest ESRD patient populations

Grassmann A et al Nephrol Dial Transplant 2005 202587-2593

Regional ESRD distributionRegion Pop GDP ESRD

million US$ (000) Prevalence pmp

EU 380 217 790Europe 804 120 393M East 271 32 150Africa 833 10 55LAmerica 512 38 310Asia 3316 11 55Japan 127 376 1830NAmerica 310 295 1400

Moeller S et al Nephrol Dial Transplant 2002 Dec17(12)2071-6

Morelinkage

withGDP

than the general

population

China Future Dialysis Expense

￥0

￥5

￥10

￥15

￥20

￥25

￥30

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Bill

ions

Ann

ual E

xpen

ditu

re o

n D

ialy

sis

￥7143670260

￥29087632671Factors98 dialysis population growth per yearModality share remains 90 HD 10 PD

Source amp Courtesy CMIA 2006 data

(From 71 billion in 2005 to 29 billion in 2020)

TIME December 8 2003Newsweek Sept 4 2000

Percentage of incident patients

with diabetes 2006

data presented only for those countries from which relevant information was available All rates are unadjusted ^UK England Wales amp Northern Ireland (Scotland data reported separately) Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only Latest data for Canada Croatia amp Italy are for 2005 Data for France include 13 regions in 2005 amp 15 regions in 2006

1 Malaysia 5752 Mexico 4993 USA 4434 Japan 4255 Taiwan 424

8 Hong Kong 41

18 Australia 324

USRDS 2008

Diagnosis Distribution of NEW patients 2006 - 2007GN

217

Obstructive28

Unknown179

DM393

Others38

HTvascular106

Inherited cong30

Infection reflux08

新症病人之病因 (2006-7)

感染

遺傳

尿道阻塞

高血壓糖尿病

腎小球腎炎

DM 393

GN 217

Hong Kong Renal Registry香港醫院管理局腎病註冊

World

20002030

154 m370 m

55 m84 m

Developed Developing

99 m286 m

167338

329

182

524307

28391

809

228

423

186

09 16

20002030

In million subjects

102

81

71

211

255

127

78

THE GLOBAL BURDEN OF DIABETES (2000-2030)

WHO March 2003

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Consensus Workshop

Part 1 Detection of chronic kidney disease

Part 2 Evaluation and estimating progression of chronic kidney disease

Part 3 Measures to prevent the progression of chronic kidney disease

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)s2-7

Summary of the Consensus Statements (1)Summary of the Consensus Statements (1)

bull It is recommended to establish a global surveillance center (ISN Kidney Disease Data Centre or ISN KDDC) to coordinate worldwide standardized screening studies with standardized screening techniques in appropriate target groups to allow for the collection of clearly comparable data

bull It is recommended that patients diagnosed with diabetes and hypertension

should have regular screening for development of kidney disease

bull It is recommended that close relatives of patients with nephropathy due to diabetes hypertension and glomerulonephritis should also be the primary targets for screening to detect clinically silent kidney disease

bull No consensus was made on an exact age ldquocut-offrdquo for initiating CKD screening

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

SHAREScreening for Hong Kong Asymptomatic Renal

Population and Evaluation programme

普查計劃

腎康體健

Li PKT et al Kidney Int 2005 Apr(94)s36-40

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Incidence of ESRD 2006

Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only

USRDS 2008

1 Taiwan 4182 USA 3633 Mexico 3464 Shanghai 2825 Japan 275

22 HK 140

30 NZ 11531 Australia 115

Prevalence of ESRD 2006

Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only

1 Taiwan 22262 Japan 19563 USA 16414 Germany 1114

7 HK 994

18 NZ 77819 Australia778

USRDS 2008

Age-specific prevalence of CKD (per 100 individuals) from 1996 to 2003 and incidence (per 100 person-years) from 1997 to 2003

Kuo HW et al Am J Kidney Dis 2007 Jan49(1)46-55 Prev

alen

ce (p

er 1

00 in

divi

dual

s) I

ncid

ence

(per

100

per

son-

year

s)

Year

Incidence

75+

65-74

45-64

20-44

0-19

Odds Ratio of 1395 for ge75 years compared with lt 20 years

Epidemiological features of CKD in Taiwan Epidemiological features of CKD in Taiwan bull 200000 individuals randomly sampled from 1996 to 2003

bull The prevalence CKD increased from 199 in 1996 to 983 in 2003

bull The overall incidence rate during 1997 to 2003 was 135100 person-years

bull Age is a key predictor of CKD ndash Odds Ratio of 1395 for age ge75 years compared with age lt 20

years

bull Other risk factors of CKD ndash diabetes ndash hypertension ndash hyperlipidemiandash female sex

Kuo HW et al Am J Kidney Dis 2007 Jan49(1)46-55

NEOERICA dataNHANES data

00402lt 15 (or on dialysis)

5020215 ndash 294464330 ndash 593

3060 ndash 892

33ge 901

UK Prevalence ()

US PopulationPrevalence ()

GFR mlmin173 m2

CKDStage

Coresh J et al Am J Kidney Dis 2003 41 1-12De Lusignan S et al Fam Pract 2005 22 234-41

Lifetime cumulative risks for ESRD Lifetime cumulative risks for ESRD

Kiberd B J Am Soc Nephrol 2006 Nov17(11)2967-73

8 for black women

3 for white men

78 for black men

22 for white women

CHINA ESRD StatusCHINA ESRD Status

bull About 75000 ESRD patients in Mainland China are receiving treatment today

bull Nearly 2 million patients may be untreated

bull The rate of growth of treated ESRD patients is 10-12 per year

bull ESRD treatments are high cost

Presented in ISPD 2006 Asia Round table on Dialysis Economics from CMIA(Chinese Medical Insurance Agency)

China ESRD Growth Rate To Exceed That of Population

1150000000

1200000000

1250000000

1300000000

1350000000

1400000000

1450000000

1500000000

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Tota

l Pop

ulat

ion

0

50000

100000

150000

200000

250000

300000

350000

ESR

D P

atie

nts

Population Dialysis patients

ACTUAL PROJECTED

ESRD Patients07 per year

~10-12 per year

Population

Source amp CourtesyCMIA 2006 data

Incidence of ESRF (for 12 months ending 31032007) 1074 (164 pmp)

641697

789 798 830885

1019 1012960

1045 1040 1074

0100200300400500600700800900

100011001200

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

Incidence of ESRF on RRT

Hong Kong Renal Registry香港醫院管理局腎病註冊

Incidence of ESRD (pmp) by age 2005

USRDS 2007

0-19 20-44 45-64 65-74 gt75

No14 No 4 No 5 No 8 No 24

(Japan - no data)

No of patient on renal replacement therapy 7160 ( 1025 pmp)

Hong Kong Renal Registry香港醫院管理局腎病註冊1998rarr2008 uarr 19 times

The reasons of this growth are

ndash Global ageing

ndash Multi-morbid population

ndash Higher life-expectancy of ESRD patients

ndash Increasing access of younger people in countries in which RRT has been limited until today

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Lung Cancer

KidneyFailure

ColonCancer

BreastCancer

Prostate Cancer

57

99

4232

Kidney Failure Compared to Cancer Deaths in the US in 2000

(in Thousands)157

SEER 2003(Surveillance Epidemiology and End Results)

1200

600

0

Ten

year

med

ical

cos

ts o

f di

alys

is p

opul

atio

n$

( bill

ions

)

1981-1990 1991-2000 2001-2010

800

1000

$

$

$

PREDICTED DIALYSIS COST OF APPROXIMATELY $ 11 TRILLION$ 11 TRILLION FOR THE COMING DECADE

400

200

Lysaght MJ J Am Soc Nephrol 2002 13 S37-40

De Vecchi AF et al NDT 1999

Dialysis Cost Europe

25 - 38 times gt National Average

Prevalence of ESRD in 2004 versus economic welfare in the 75 Prevalence of ESRD in 2004 versus economic welfare in the 75 countries with the largest ESRD patient populationscountries with the largest ESRD patient populations

Grassmann A et al Nephrol Dial Transplant 2005 202587-2593

Regional ESRD distributionRegion Pop GDP ESRD

million US$ (000) Prevalence pmp

EU 380 217 790Europe 804 120 393M East 271 32 150Africa 833 10 55LAmerica 512 38 310Asia 3316 11 55Japan 127 376 1830NAmerica 310 295 1400

Moeller S et al Nephrol Dial Transplant 2002 Dec17(12)2071-6

Morelinkage

withGDP

than the general

population

China Future Dialysis Expense

￥0

￥5

￥10

￥15

￥20

￥25

￥30

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Bill

ions

Ann

ual E

xpen

ditu

re o

n D

ialy

sis

￥7143670260

￥29087632671Factors98 dialysis population growth per yearModality share remains 90 HD 10 PD

Source amp Courtesy CMIA 2006 data

(From 71 billion in 2005 to 29 billion in 2020)

TIME December 8 2003Newsweek Sept 4 2000

Percentage of incident patients

with diabetes 2006

data presented only for those countries from which relevant information was available All rates are unadjusted ^UK England Wales amp Northern Ireland (Scotland data reported separately) Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only Latest data for Canada Croatia amp Italy are for 2005 Data for France include 13 regions in 2005 amp 15 regions in 2006

1 Malaysia 5752 Mexico 4993 USA 4434 Japan 4255 Taiwan 424

8 Hong Kong 41

18 Australia 324

USRDS 2008

Diagnosis Distribution of NEW patients 2006 - 2007GN

217

Obstructive28

Unknown179

DM393

Others38

HTvascular106

Inherited cong30

Infection reflux08

新症病人之病因 (2006-7)

感染

遺傳

尿道阻塞

高血壓糖尿病

腎小球腎炎

DM 393

GN 217

Hong Kong Renal Registry香港醫院管理局腎病註冊

World

20002030

154 m370 m

55 m84 m

Developed Developing

99 m286 m

167338

329

182

524307

28391

809

228

423

186

09 16

20002030

In million subjects

102

81

71

211

255

127

78

THE GLOBAL BURDEN OF DIABETES (2000-2030)

WHO March 2003

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Consensus Workshop

Part 1 Detection of chronic kidney disease

Part 2 Evaluation and estimating progression of chronic kidney disease

Part 3 Measures to prevent the progression of chronic kidney disease

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)s2-7

Summary of the Consensus Statements (1)Summary of the Consensus Statements (1)

bull It is recommended to establish a global surveillance center (ISN Kidney Disease Data Centre or ISN KDDC) to coordinate worldwide standardized screening studies with standardized screening techniques in appropriate target groups to allow for the collection of clearly comparable data

bull It is recommended that patients diagnosed with diabetes and hypertension

should have regular screening for development of kidney disease

bull It is recommended that close relatives of patients with nephropathy due to diabetes hypertension and glomerulonephritis should also be the primary targets for screening to detect clinically silent kidney disease

bull No consensus was made on an exact age ldquocut-offrdquo for initiating CKD screening

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

SHAREScreening for Hong Kong Asymptomatic Renal

Population and Evaluation programme

普查計劃

腎康體健

Li PKT et al Kidney Int 2005 Apr(94)s36-40

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Prevalence of ESRD 2006

Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only

1 Taiwan 22262 Japan 19563 USA 16414 Germany 1114

7 HK 994

18 NZ 77819 Australia778

USRDS 2008

Age-specific prevalence of CKD (per 100 individuals) from 1996 to 2003 and incidence (per 100 person-years) from 1997 to 2003

Kuo HW et al Am J Kidney Dis 2007 Jan49(1)46-55 Prev

alen

ce (p

er 1

00 in

divi

dual

s) I

ncid

ence

(per

100

per

son-

year

s)

Year

Incidence

75+

65-74

45-64

20-44

0-19

Odds Ratio of 1395 for ge75 years compared with lt 20 years

Epidemiological features of CKD in Taiwan Epidemiological features of CKD in Taiwan bull 200000 individuals randomly sampled from 1996 to 2003

bull The prevalence CKD increased from 199 in 1996 to 983 in 2003

bull The overall incidence rate during 1997 to 2003 was 135100 person-years

bull Age is a key predictor of CKD ndash Odds Ratio of 1395 for age ge75 years compared with age lt 20

years

bull Other risk factors of CKD ndash diabetes ndash hypertension ndash hyperlipidemiandash female sex

Kuo HW et al Am J Kidney Dis 2007 Jan49(1)46-55

NEOERICA dataNHANES data

00402lt 15 (or on dialysis)

5020215 ndash 294464330 ndash 593

3060 ndash 892

33ge 901

UK Prevalence ()

US PopulationPrevalence ()

GFR mlmin173 m2

CKDStage

Coresh J et al Am J Kidney Dis 2003 41 1-12De Lusignan S et al Fam Pract 2005 22 234-41

Lifetime cumulative risks for ESRD Lifetime cumulative risks for ESRD

Kiberd B J Am Soc Nephrol 2006 Nov17(11)2967-73

8 for black women

3 for white men

78 for black men

22 for white women

CHINA ESRD StatusCHINA ESRD Status

bull About 75000 ESRD patients in Mainland China are receiving treatment today

bull Nearly 2 million patients may be untreated

bull The rate of growth of treated ESRD patients is 10-12 per year

bull ESRD treatments are high cost

Presented in ISPD 2006 Asia Round table on Dialysis Economics from CMIA(Chinese Medical Insurance Agency)

China ESRD Growth Rate To Exceed That of Population

1150000000

1200000000

1250000000

1300000000

1350000000

1400000000

1450000000

1500000000

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Tota

l Pop

ulat

ion

0

50000

100000

150000

200000

250000

300000

350000

ESR

D P

atie

nts

Population Dialysis patients

ACTUAL PROJECTED

ESRD Patients07 per year

~10-12 per year

Population

Source amp CourtesyCMIA 2006 data

Incidence of ESRF (for 12 months ending 31032007) 1074 (164 pmp)

641697

789 798 830885

1019 1012960

1045 1040 1074

0100200300400500600700800900

100011001200

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

Incidence of ESRF on RRT

Hong Kong Renal Registry香港醫院管理局腎病註冊

Incidence of ESRD (pmp) by age 2005

USRDS 2007

0-19 20-44 45-64 65-74 gt75

No14 No 4 No 5 No 8 No 24

(Japan - no data)

No of patient on renal replacement therapy 7160 ( 1025 pmp)

Hong Kong Renal Registry香港醫院管理局腎病註冊1998rarr2008 uarr 19 times

The reasons of this growth are

ndash Global ageing

ndash Multi-morbid population

ndash Higher life-expectancy of ESRD patients

ndash Increasing access of younger people in countries in which RRT has been limited until today

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Lung Cancer

KidneyFailure

ColonCancer

BreastCancer

Prostate Cancer

57

99

4232

Kidney Failure Compared to Cancer Deaths in the US in 2000

(in Thousands)157

SEER 2003(Surveillance Epidemiology and End Results)

1200

600

0

Ten

year

med

ical

cos

ts o

f di

alys

is p

opul

atio

n$

( bill

ions

)

1981-1990 1991-2000 2001-2010

800

1000

$

$

$

PREDICTED DIALYSIS COST OF APPROXIMATELY $ 11 TRILLION$ 11 TRILLION FOR THE COMING DECADE

400

200

Lysaght MJ J Am Soc Nephrol 2002 13 S37-40

De Vecchi AF et al NDT 1999

Dialysis Cost Europe

25 - 38 times gt National Average

Prevalence of ESRD in 2004 versus economic welfare in the 75 Prevalence of ESRD in 2004 versus economic welfare in the 75 countries with the largest ESRD patient populationscountries with the largest ESRD patient populations

Grassmann A et al Nephrol Dial Transplant 2005 202587-2593

Regional ESRD distributionRegion Pop GDP ESRD

million US$ (000) Prevalence pmp

EU 380 217 790Europe 804 120 393M East 271 32 150Africa 833 10 55LAmerica 512 38 310Asia 3316 11 55Japan 127 376 1830NAmerica 310 295 1400

Moeller S et al Nephrol Dial Transplant 2002 Dec17(12)2071-6

Morelinkage

withGDP

than the general

population

China Future Dialysis Expense

￥0

￥5

￥10

￥15

￥20

￥25

￥30

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Bill

ions

Ann

ual E

xpen

ditu

re o

n D

ialy

sis

￥7143670260

￥29087632671Factors98 dialysis population growth per yearModality share remains 90 HD 10 PD

Source amp Courtesy CMIA 2006 data

(From 71 billion in 2005 to 29 billion in 2020)

TIME December 8 2003Newsweek Sept 4 2000

Percentage of incident patients

with diabetes 2006

data presented only for those countries from which relevant information was available All rates are unadjusted ^UK England Wales amp Northern Ireland (Scotland data reported separately) Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only Latest data for Canada Croatia amp Italy are for 2005 Data for France include 13 regions in 2005 amp 15 regions in 2006

1 Malaysia 5752 Mexico 4993 USA 4434 Japan 4255 Taiwan 424

8 Hong Kong 41

18 Australia 324

USRDS 2008

Diagnosis Distribution of NEW patients 2006 - 2007GN

217

Obstructive28

Unknown179

DM393

Others38

HTvascular106

Inherited cong30

Infection reflux08

新症病人之病因 (2006-7)

感染

遺傳

尿道阻塞

高血壓糖尿病

腎小球腎炎

DM 393

GN 217

Hong Kong Renal Registry香港醫院管理局腎病註冊

World

20002030

154 m370 m

55 m84 m

Developed Developing

99 m286 m

167338

329

182

524307

28391

809

228

423

186

09 16

20002030

In million subjects

102

81

71

211

255

127

78

THE GLOBAL BURDEN OF DIABETES (2000-2030)

WHO March 2003

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Consensus Workshop

Part 1 Detection of chronic kidney disease

Part 2 Evaluation and estimating progression of chronic kidney disease

Part 3 Measures to prevent the progression of chronic kidney disease

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)s2-7

Summary of the Consensus Statements (1)Summary of the Consensus Statements (1)

bull It is recommended to establish a global surveillance center (ISN Kidney Disease Data Centre or ISN KDDC) to coordinate worldwide standardized screening studies with standardized screening techniques in appropriate target groups to allow for the collection of clearly comparable data

bull It is recommended that patients diagnosed with diabetes and hypertension

should have regular screening for development of kidney disease

bull It is recommended that close relatives of patients with nephropathy due to diabetes hypertension and glomerulonephritis should also be the primary targets for screening to detect clinically silent kidney disease

bull No consensus was made on an exact age ldquocut-offrdquo for initiating CKD screening

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

SHAREScreening for Hong Kong Asymptomatic Renal

Population and Evaluation programme

普查計劃

腎康體健

Li PKT et al Kidney Int 2005 Apr(94)s36-40

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Age-specific prevalence of CKD (per 100 individuals) from 1996 to 2003 and incidence (per 100 person-years) from 1997 to 2003

Kuo HW et al Am J Kidney Dis 2007 Jan49(1)46-55 Prev

alen

ce (p

er 1

00 in

divi

dual

s) I

ncid

ence

(per

100

per

son-

year

s)

Year

Incidence

75+

65-74

45-64

20-44

0-19

Odds Ratio of 1395 for ge75 years compared with lt 20 years

Epidemiological features of CKD in Taiwan Epidemiological features of CKD in Taiwan bull 200000 individuals randomly sampled from 1996 to 2003

bull The prevalence CKD increased from 199 in 1996 to 983 in 2003

bull The overall incidence rate during 1997 to 2003 was 135100 person-years

bull Age is a key predictor of CKD ndash Odds Ratio of 1395 for age ge75 years compared with age lt 20

years

bull Other risk factors of CKD ndash diabetes ndash hypertension ndash hyperlipidemiandash female sex

Kuo HW et al Am J Kidney Dis 2007 Jan49(1)46-55

NEOERICA dataNHANES data

00402lt 15 (or on dialysis)

5020215 ndash 294464330 ndash 593

3060 ndash 892

33ge 901

UK Prevalence ()

US PopulationPrevalence ()

GFR mlmin173 m2

CKDStage

Coresh J et al Am J Kidney Dis 2003 41 1-12De Lusignan S et al Fam Pract 2005 22 234-41

Lifetime cumulative risks for ESRD Lifetime cumulative risks for ESRD

Kiberd B J Am Soc Nephrol 2006 Nov17(11)2967-73

8 for black women

3 for white men

78 for black men

22 for white women

CHINA ESRD StatusCHINA ESRD Status

bull About 75000 ESRD patients in Mainland China are receiving treatment today

bull Nearly 2 million patients may be untreated

bull The rate of growth of treated ESRD patients is 10-12 per year

bull ESRD treatments are high cost

Presented in ISPD 2006 Asia Round table on Dialysis Economics from CMIA(Chinese Medical Insurance Agency)

China ESRD Growth Rate To Exceed That of Population

1150000000

1200000000

1250000000

1300000000

1350000000

1400000000

1450000000

1500000000

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Tota

l Pop

ulat

ion

0

50000

100000

150000

200000

250000

300000

350000

ESR

D P

atie

nts

Population Dialysis patients

ACTUAL PROJECTED

ESRD Patients07 per year

~10-12 per year

Population

Source amp CourtesyCMIA 2006 data

Incidence of ESRF (for 12 months ending 31032007) 1074 (164 pmp)

641697

789 798 830885

1019 1012960

1045 1040 1074

0100200300400500600700800900

100011001200

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

Incidence of ESRF on RRT

Hong Kong Renal Registry香港醫院管理局腎病註冊

Incidence of ESRD (pmp) by age 2005

USRDS 2007

0-19 20-44 45-64 65-74 gt75

No14 No 4 No 5 No 8 No 24

(Japan - no data)

No of patient on renal replacement therapy 7160 ( 1025 pmp)

Hong Kong Renal Registry香港醫院管理局腎病註冊1998rarr2008 uarr 19 times

The reasons of this growth are

ndash Global ageing

ndash Multi-morbid population

ndash Higher life-expectancy of ESRD patients

ndash Increasing access of younger people in countries in which RRT has been limited until today

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Lung Cancer

KidneyFailure

ColonCancer

BreastCancer

Prostate Cancer

57

99

4232

Kidney Failure Compared to Cancer Deaths in the US in 2000

(in Thousands)157

SEER 2003(Surveillance Epidemiology and End Results)

1200

600

0

Ten

year

med

ical

cos

ts o

f di

alys

is p

opul

atio

n$

( bill

ions

)

1981-1990 1991-2000 2001-2010

800

1000

$

$

$

PREDICTED DIALYSIS COST OF APPROXIMATELY $ 11 TRILLION$ 11 TRILLION FOR THE COMING DECADE

400

200

Lysaght MJ J Am Soc Nephrol 2002 13 S37-40

De Vecchi AF et al NDT 1999

Dialysis Cost Europe

25 - 38 times gt National Average

Prevalence of ESRD in 2004 versus economic welfare in the 75 Prevalence of ESRD in 2004 versus economic welfare in the 75 countries with the largest ESRD patient populationscountries with the largest ESRD patient populations

Grassmann A et al Nephrol Dial Transplant 2005 202587-2593

Regional ESRD distributionRegion Pop GDP ESRD

million US$ (000) Prevalence pmp

EU 380 217 790Europe 804 120 393M East 271 32 150Africa 833 10 55LAmerica 512 38 310Asia 3316 11 55Japan 127 376 1830NAmerica 310 295 1400

Moeller S et al Nephrol Dial Transplant 2002 Dec17(12)2071-6

Morelinkage

withGDP

than the general

population

China Future Dialysis Expense

￥0

￥5

￥10

￥15

￥20

￥25

￥30

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Bill

ions

Ann

ual E

xpen

ditu

re o

n D

ialy

sis

￥7143670260

￥29087632671Factors98 dialysis population growth per yearModality share remains 90 HD 10 PD

Source amp Courtesy CMIA 2006 data

(From 71 billion in 2005 to 29 billion in 2020)

TIME December 8 2003Newsweek Sept 4 2000

Percentage of incident patients

with diabetes 2006

data presented only for those countries from which relevant information was available All rates are unadjusted ^UK England Wales amp Northern Ireland (Scotland data reported separately) Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only Latest data for Canada Croatia amp Italy are for 2005 Data for France include 13 regions in 2005 amp 15 regions in 2006

1 Malaysia 5752 Mexico 4993 USA 4434 Japan 4255 Taiwan 424

8 Hong Kong 41

18 Australia 324

USRDS 2008

Diagnosis Distribution of NEW patients 2006 - 2007GN

217

Obstructive28

Unknown179

DM393

Others38

HTvascular106

Inherited cong30

Infection reflux08

新症病人之病因 (2006-7)

感染

遺傳

尿道阻塞

高血壓糖尿病

腎小球腎炎

DM 393

GN 217

Hong Kong Renal Registry香港醫院管理局腎病註冊

World

20002030

154 m370 m

55 m84 m

Developed Developing

99 m286 m

167338

329

182

524307

28391

809

228

423

186

09 16

20002030

In million subjects

102

81

71

211

255

127

78

THE GLOBAL BURDEN OF DIABETES (2000-2030)

WHO March 2003

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Consensus Workshop

Part 1 Detection of chronic kidney disease

Part 2 Evaluation and estimating progression of chronic kidney disease

Part 3 Measures to prevent the progression of chronic kidney disease

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)s2-7

Summary of the Consensus Statements (1)Summary of the Consensus Statements (1)

bull It is recommended to establish a global surveillance center (ISN Kidney Disease Data Centre or ISN KDDC) to coordinate worldwide standardized screening studies with standardized screening techniques in appropriate target groups to allow for the collection of clearly comparable data

bull It is recommended that patients diagnosed with diabetes and hypertension

should have regular screening for development of kidney disease

bull It is recommended that close relatives of patients with nephropathy due to diabetes hypertension and glomerulonephritis should also be the primary targets for screening to detect clinically silent kidney disease

bull No consensus was made on an exact age ldquocut-offrdquo for initiating CKD screening

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

SHAREScreening for Hong Kong Asymptomatic Renal

Population and Evaluation programme

普查計劃

腎康體健

Li PKT et al Kidney Int 2005 Apr(94)s36-40

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Epidemiological features of CKD in Taiwan Epidemiological features of CKD in Taiwan bull 200000 individuals randomly sampled from 1996 to 2003

bull The prevalence CKD increased from 199 in 1996 to 983 in 2003

bull The overall incidence rate during 1997 to 2003 was 135100 person-years

bull Age is a key predictor of CKD ndash Odds Ratio of 1395 for age ge75 years compared with age lt 20

years

bull Other risk factors of CKD ndash diabetes ndash hypertension ndash hyperlipidemiandash female sex

Kuo HW et al Am J Kidney Dis 2007 Jan49(1)46-55

NEOERICA dataNHANES data

00402lt 15 (or on dialysis)

5020215 ndash 294464330 ndash 593

3060 ndash 892

33ge 901

UK Prevalence ()

US PopulationPrevalence ()

GFR mlmin173 m2

CKDStage

Coresh J et al Am J Kidney Dis 2003 41 1-12De Lusignan S et al Fam Pract 2005 22 234-41

Lifetime cumulative risks for ESRD Lifetime cumulative risks for ESRD

Kiberd B J Am Soc Nephrol 2006 Nov17(11)2967-73

8 for black women

3 for white men

78 for black men

22 for white women

CHINA ESRD StatusCHINA ESRD Status

bull About 75000 ESRD patients in Mainland China are receiving treatment today

bull Nearly 2 million patients may be untreated

bull The rate of growth of treated ESRD patients is 10-12 per year

bull ESRD treatments are high cost

Presented in ISPD 2006 Asia Round table on Dialysis Economics from CMIA(Chinese Medical Insurance Agency)

China ESRD Growth Rate To Exceed That of Population

1150000000

1200000000

1250000000

1300000000

1350000000

1400000000

1450000000

1500000000

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Tota

l Pop

ulat

ion

0

50000

100000

150000

200000

250000

300000

350000

ESR

D P

atie

nts

Population Dialysis patients

ACTUAL PROJECTED

ESRD Patients07 per year

~10-12 per year

Population

Source amp CourtesyCMIA 2006 data

Incidence of ESRF (for 12 months ending 31032007) 1074 (164 pmp)

641697

789 798 830885

1019 1012960

1045 1040 1074

0100200300400500600700800900

100011001200

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

Incidence of ESRF on RRT

Hong Kong Renal Registry香港醫院管理局腎病註冊

Incidence of ESRD (pmp) by age 2005

USRDS 2007

0-19 20-44 45-64 65-74 gt75

No14 No 4 No 5 No 8 No 24

(Japan - no data)

No of patient on renal replacement therapy 7160 ( 1025 pmp)

Hong Kong Renal Registry香港醫院管理局腎病註冊1998rarr2008 uarr 19 times

The reasons of this growth are

ndash Global ageing

ndash Multi-morbid population

ndash Higher life-expectancy of ESRD patients

ndash Increasing access of younger people in countries in which RRT has been limited until today

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Lung Cancer

KidneyFailure

ColonCancer

BreastCancer

Prostate Cancer

57

99

4232

Kidney Failure Compared to Cancer Deaths in the US in 2000

(in Thousands)157

SEER 2003(Surveillance Epidemiology and End Results)

1200

600

0

Ten

year

med

ical

cos

ts o

f di

alys

is p

opul

atio

n$

( bill

ions

)

1981-1990 1991-2000 2001-2010

800

1000

$

$

$

PREDICTED DIALYSIS COST OF APPROXIMATELY $ 11 TRILLION$ 11 TRILLION FOR THE COMING DECADE

400

200

Lysaght MJ J Am Soc Nephrol 2002 13 S37-40

De Vecchi AF et al NDT 1999

Dialysis Cost Europe

25 - 38 times gt National Average

Prevalence of ESRD in 2004 versus economic welfare in the 75 Prevalence of ESRD in 2004 versus economic welfare in the 75 countries with the largest ESRD patient populationscountries with the largest ESRD patient populations

Grassmann A et al Nephrol Dial Transplant 2005 202587-2593

Regional ESRD distributionRegion Pop GDP ESRD

million US$ (000) Prevalence pmp

EU 380 217 790Europe 804 120 393M East 271 32 150Africa 833 10 55LAmerica 512 38 310Asia 3316 11 55Japan 127 376 1830NAmerica 310 295 1400

Moeller S et al Nephrol Dial Transplant 2002 Dec17(12)2071-6

Morelinkage

withGDP

than the general

population

China Future Dialysis Expense

￥0

￥5

￥10

￥15

￥20

￥25

￥30

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Bill

ions

Ann

ual E

xpen

ditu

re o

n D

ialy

sis

￥7143670260

￥29087632671Factors98 dialysis population growth per yearModality share remains 90 HD 10 PD

Source amp Courtesy CMIA 2006 data

(From 71 billion in 2005 to 29 billion in 2020)

TIME December 8 2003Newsweek Sept 4 2000

Percentage of incident patients

with diabetes 2006

data presented only for those countries from which relevant information was available All rates are unadjusted ^UK England Wales amp Northern Ireland (Scotland data reported separately) Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only Latest data for Canada Croatia amp Italy are for 2005 Data for France include 13 regions in 2005 amp 15 regions in 2006

1 Malaysia 5752 Mexico 4993 USA 4434 Japan 4255 Taiwan 424

8 Hong Kong 41

18 Australia 324

USRDS 2008

Diagnosis Distribution of NEW patients 2006 - 2007GN

217

Obstructive28

Unknown179

DM393

Others38

HTvascular106

Inherited cong30

Infection reflux08

新症病人之病因 (2006-7)

感染

遺傳

尿道阻塞

高血壓糖尿病

腎小球腎炎

DM 393

GN 217

Hong Kong Renal Registry香港醫院管理局腎病註冊

World

20002030

154 m370 m

55 m84 m

Developed Developing

99 m286 m

167338

329

182

524307

28391

809

228

423

186

09 16

20002030

In million subjects

102

81

71

211

255

127

78

THE GLOBAL BURDEN OF DIABETES (2000-2030)

WHO March 2003

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Consensus Workshop

Part 1 Detection of chronic kidney disease

Part 2 Evaluation and estimating progression of chronic kidney disease

Part 3 Measures to prevent the progression of chronic kidney disease

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)s2-7

Summary of the Consensus Statements (1)Summary of the Consensus Statements (1)

bull It is recommended to establish a global surveillance center (ISN Kidney Disease Data Centre or ISN KDDC) to coordinate worldwide standardized screening studies with standardized screening techniques in appropriate target groups to allow for the collection of clearly comparable data

bull It is recommended that patients diagnosed with diabetes and hypertension

should have regular screening for development of kidney disease

bull It is recommended that close relatives of patients with nephropathy due to diabetes hypertension and glomerulonephritis should also be the primary targets for screening to detect clinically silent kidney disease

bull No consensus was made on an exact age ldquocut-offrdquo for initiating CKD screening

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

SHAREScreening for Hong Kong Asymptomatic Renal

Population and Evaluation programme

普查計劃

腎康體健

Li PKT et al Kidney Int 2005 Apr(94)s36-40

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

NEOERICA dataNHANES data

00402lt 15 (or on dialysis)

5020215 ndash 294464330 ndash 593

3060 ndash 892

33ge 901

UK Prevalence ()

US PopulationPrevalence ()

GFR mlmin173 m2

CKDStage

Coresh J et al Am J Kidney Dis 2003 41 1-12De Lusignan S et al Fam Pract 2005 22 234-41

Lifetime cumulative risks for ESRD Lifetime cumulative risks for ESRD

Kiberd B J Am Soc Nephrol 2006 Nov17(11)2967-73

8 for black women

3 for white men

78 for black men

22 for white women

CHINA ESRD StatusCHINA ESRD Status

bull About 75000 ESRD patients in Mainland China are receiving treatment today

bull Nearly 2 million patients may be untreated

bull The rate of growth of treated ESRD patients is 10-12 per year

bull ESRD treatments are high cost

Presented in ISPD 2006 Asia Round table on Dialysis Economics from CMIA(Chinese Medical Insurance Agency)

China ESRD Growth Rate To Exceed That of Population

1150000000

1200000000

1250000000

1300000000

1350000000

1400000000

1450000000

1500000000

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Tota

l Pop

ulat

ion

0

50000

100000

150000

200000

250000

300000

350000

ESR

D P

atie

nts

Population Dialysis patients

ACTUAL PROJECTED

ESRD Patients07 per year

~10-12 per year

Population

Source amp CourtesyCMIA 2006 data

Incidence of ESRF (for 12 months ending 31032007) 1074 (164 pmp)

641697

789 798 830885

1019 1012960

1045 1040 1074

0100200300400500600700800900

100011001200

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

Incidence of ESRF on RRT

Hong Kong Renal Registry香港醫院管理局腎病註冊

Incidence of ESRD (pmp) by age 2005

USRDS 2007

0-19 20-44 45-64 65-74 gt75

No14 No 4 No 5 No 8 No 24

(Japan - no data)

No of patient on renal replacement therapy 7160 ( 1025 pmp)

Hong Kong Renal Registry香港醫院管理局腎病註冊1998rarr2008 uarr 19 times

The reasons of this growth are

ndash Global ageing

ndash Multi-morbid population

ndash Higher life-expectancy of ESRD patients

ndash Increasing access of younger people in countries in which RRT has been limited until today

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Lung Cancer

KidneyFailure

ColonCancer

BreastCancer

Prostate Cancer

57

99

4232

Kidney Failure Compared to Cancer Deaths in the US in 2000

(in Thousands)157

SEER 2003(Surveillance Epidemiology and End Results)

1200

600

0

Ten

year

med

ical

cos

ts o

f di

alys

is p

opul

atio

n$

( bill

ions

)

1981-1990 1991-2000 2001-2010

800

1000

$

$

$

PREDICTED DIALYSIS COST OF APPROXIMATELY $ 11 TRILLION$ 11 TRILLION FOR THE COMING DECADE

400

200

Lysaght MJ J Am Soc Nephrol 2002 13 S37-40

De Vecchi AF et al NDT 1999

Dialysis Cost Europe

25 - 38 times gt National Average

Prevalence of ESRD in 2004 versus economic welfare in the 75 Prevalence of ESRD in 2004 versus economic welfare in the 75 countries with the largest ESRD patient populationscountries with the largest ESRD patient populations

Grassmann A et al Nephrol Dial Transplant 2005 202587-2593

Regional ESRD distributionRegion Pop GDP ESRD

million US$ (000) Prevalence pmp

EU 380 217 790Europe 804 120 393M East 271 32 150Africa 833 10 55LAmerica 512 38 310Asia 3316 11 55Japan 127 376 1830NAmerica 310 295 1400

Moeller S et al Nephrol Dial Transplant 2002 Dec17(12)2071-6

Morelinkage

withGDP

than the general

population

China Future Dialysis Expense

￥0

￥5

￥10

￥15

￥20

￥25

￥30

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Bill

ions

Ann

ual E

xpen

ditu

re o

n D

ialy

sis

￥7143670260

￥29087632671Factors98 dialysis population growth per yearModality share remains 90 HD 10 PD

Source amp Courtesy CMIA 2006 data

(From 71 billion in 2005 to 29 billion in 2020)

TIME December 8 2003Newsweek Sept 4 2000

Percentage of incident patients

with diabetes 2006

data presented only for those countries from which relevant information was available All rates are unadjusted ^UK England Wales amp Northern Ireland (Scotland data reported separately) Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only Latest data for Canada Croatia amp Italy are for 2005 Data for France include 13 regions in 2005 amp 15 regions in 2006

1 Malaysia 5752 Mexico 4993 USA 4434 Japan 4255 Taiwan 424

8 Hong Kong 41

18 Australia 324

USRDS 2008

Diagnosis Distribution of NEW patients 2006 - 2007GN

217

Obstructive28

Unknown179

DM393

Others38

HTvascular106

Inherited cong30

Infection reflux08

新症病人之病因 (2006-7)

感染

遺傳

尿道阻塞

高血壓糖尿病

腎小球腎炎

DM 393

GN 217

Hong Kong Renal Registry香港醫院管理局腎病註冊

World

20002030

154 m370 m

55 m84 m

Developed Developing

99 m286 m

167338

329

182

524307

28391

809

228

423

186

09 16

20002030

In million subjects

102

81

71

211

255

127

78

THE GLOBAL BURDEN OF DIABETES (2000-2030)

WHO March 2003

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Consensus Workshop

Part 1 Detection of chronic kidney disease

Part 2 Evaluation and estimating progression of chronic kidney disease

Part 3 Measures to prevent the progression of chronic kidney disease

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)s2-7

Summary of the Consensus Statements (1)Summary of the Consensus Statements (1)

bull It is recommended to establish a global surveillance center (ISN Kidney Disease Data Centre or ISN KDDC) to coordinate worldwide standardized screening studies with standardized screening techniques in appropriate target groups to allow for the collection of clearly comparable data

bull It is recommended that patients diagnosed with diabetes and hypertension

should have regular screening for development of kidney disease

bull It is recommended that close relatives of patients with nephropathy due to diabetes hypertension and glomerulonephritis should also be the primary targets for screening to detect clinically silent kidney disease

bull No consensus was made on an exact age ldquocut-offrdquo for initiating CKD screening

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

SHAREScreening for Hong Kong Asymptomatic Renal

Population and Evaluation programme

普查計劃

腎康體健

Li PKT et al Kidney Int 2005 Apr(94)s36-40

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Lifetime cumulative risks for ESRD Lifetime cumulative risks for ESRD

Kiberd B J Am Soc Nephrol 2006 Nov17(11)2967-73

8 for black women

3 for white men

78 for black men

22 for white women

CHINA ESRD StatusCHINA ESRD Status

bull About 75000 ESRD patients in Mainland China are receiving treatment today

bull Nearly 2 million patients may be untreated

bull The rate of growth of treated ESRD patients is 10-12 per year

bull ESRD treatments are high cost

Presented in ISPD 2006 Asia Round table on Dialysis Economics from CMIA(Chinese Medical Insurance Agency)

China ESRD Growth Rate To Exceed That of Population

1150000000

1200000000

1250000000

1300000000

1350000000

1400000000

1450000000

1500000000

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Tota

l Pop

ulat

ion

0

50000

100000

150000

200000

250000

300000

350000

ESR

D P

atie

nts

Population Dialysis patients

ACTUAL PROJECTED

ESRD Patients07 per year

~10-12 per year

Population

Source amp CourtesyCMIA 2006 data

Incidence of ESRF (for 12 months ending 31032007) 1074 (164 pmp)

641697

789 798 830885

1019 1012960

1045 1040 1074

0100200300400500600700800900

100011001200

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

Incidence of ESRF on RRT

Hong Kong Renal Registry香港醫院管理局腎病註冊

Incidence of ESRD (pmp) by age 2005

USRDS 2007

0-19 20-44 45-64 65-74 gt75

No14 No 4 No 5 No 8 No 24

(Japan - no data)

No of patient on renal replacement therapy 7160 ( 1025 pmp)

Hong Kong Renal Registry香港醫院管理局腎病註冊1998rarr2008 uarr 19 times

The reasons of this growth are

ndash Global ageing

ndash Multi-morbid population

ndash Higher life-expectancy of ESRD patients

ndash Increasing access of younger people in countries in which RRT has been limited until today

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Lung Cancer

KidneyFailure

ColonCancer

BreastCancer

Prostate Cancer

57

99

4232

Kidney Failure Compared to Cancer Deaths in the US in 2000

(in Thousands)157

SEER 2003(Surveillance Epidemiology and End Results)

1200

600

0

Ten

year

med

ical

cos

ts o

f di

alys

is p

opul

atio

n$

( bill

ions

)

1981-1990 1991-2000 2001-2010

800

1000

$

$

$

PREDICTED DIALYSIS COST OF APPROXIMATELY $ 11 TRILLION$ 11 TRILLION FOR THE COMING DECADE

400

200

Lysaght MJ J Am Soc Nephrol 2002 13 S37-40

De Vecchi AF et al NDT 1999

Dialysis Cost Europe

25 - 38 times gt National Average

Prevalence of ESRD in 2004 versus economic welfare in the 75 Prevalence of ESRD in 2004 versus economic welfare in the 75 countries with the largest ESRD patient populationscountries with the largest ESRD patient populations

Grassmann A et al Nephrol Dial Transplant 2005 202587-2593

Regional ESRD distributionRegion Pop GDP ESRD

million US$ (000) Prevalence pmp

EU 380 217 790Europe 804 120 393M East 271 32 150Africa 833 10 55LAmerica 512 38 310Asia 3316 11 55Japan 127 376 1830NAmerica 310 295 1400

Moeller S et al Nephrol Dial Transplant 2002 Dec17(12)2071-6

Morelinkage

withGDP

than the general

population

China Future Dialysis Expense

￥0

￥5

￥10

￥15

￥20

￥25

￥30

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Bill

ions

Ann

ual E

xpen

ditu

re o

n D

ialy

sis

￥7143670260

￥29087632671Factors98 dialysis population growth per yearModality share remains 90 HD 10 PD

Source amp Courtesy CMIA 2006 data

(From 71 billion in 2005 to 29 billion in 2020)

TIME December 8 2003Newsweek Sept 4 2000

Percentage of incident patients

with diabetes 2006

data presented only for those countries from which relevant information was available All rates are unadjusted ^UK England Wales amp Northern Ireland (Scotland data reported separately) Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only Latest data for Canada Croatia amp Italy are for 2005 Data for France include 13 regions in 2005 amp 15 regions in 2006

1 Malaysia 5752 Mexico 4993 USA 4434 Japan 4255 Taiwan 424

8 Hong Kong 41

18 Australia 324

USRDS 2008

Diagnosis Distribution of NEW patients 2006 - 2007GN

217

Obstructive28

Unknown179

DM393

Others38

HTvascular106

Inherited cong30

Infection reflux08

新症病人之病因 (2006-7)

感染

遺傳

尿道阻塞

高血壓糖尿病

腎小球腎炎

DM 393

GN 217

Hong Kong Renal Registry香港醫院管理局腎病註冊

World

20002030

154 m370 m

55 m84 m

Developed Developing

99 m286 m

167338

329

182

524307

28391

809

228

423

186

09 16

20002030

In million subjects

102

81

71

211

255

127

78

THE GLOBAL BURDEN OF DIABETES (2000-2030)

WHO March 2003

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Consensus Workshop

Part 1 Detection of chronic kidney disease

Part 2 Evaluation and estimating progression of chronic kidney disease

Part 3 Measures to prevent the progression of chronic kidney disease

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)s2-7

Summary of the Consensus Statements (1)Summary of the Consensus Statements (1)

bull It is recommended to establish a global surveillance center (ISN Kidney Disease Data Centre or ISN KDDC) to coordinate worldwide standardized screening studies with standardized screening techniques in appropriate target groups to allow for the collection of clearly comparable data

bull It is recommended that patients diagnosed with diabetes and hypertension

should have regular screening for development of kidney disease

bull It is recommended that close relatives of patients with nephropathy due to diabetes hypertension and glomerulonephritis should also be the primary targets for screening to detect clinically silent kidney disease

bull No consensus was made on an exact age ldquocut-offrdquo for initiating CKD screening

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

SHAREScreening for Hong Kong Asymptomatic Renal

Population and Evaluation programme

普查計劃

腎康體健

Li PKT et al Kidney Int 2005 Apr(94)s36-40

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

CHINA ESRD StatusCHINA ESRD Status

bull About 75000 ESRD patients in Mainland China are receiving treatment today

bull Nearly 2 million patients may be untreated

bull The rate of growth of treated ESRD patients is 10-12 per year

bull ESRD treatments are high cost

Presented in ISPD 2006 Asia Round table on Dialysis Economics from CMIA(Chinese Medical Insurance Agency)

China ESRD Growth Rate To Exceed That of Population

1150000000

1200000000

1250000000

1300000000

1350000000

1400000000

1450000000

1500000000

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Tota

l Pop

ulat

ion

0

50000

100000

150000

200000

250000

300000

350000

ESR

D P

atie

nts

Population Dialysis patients

ACTUAL PROJECTED

ESRD Patients07 per year

~10-12 per year

Population

Source amp CourtesyCMIA 2006 data

Incidence of ESRF (for 12 months ending 31032007) 1074 (164 pmp)

641697

789 798 830885

1019 1012960

1045 1040 1074

0100200300400500600700800900

100011001200

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

Incidence of ESRF on RRT

Hong Kong Renal Registry香港醫院管理局腎病註冊

Incidence of ESRD (pmp) by age 2005

USRDS 2007

0-19 20-44 45-64 65-74 gt75

No14 No 4 No 5 No 8 No 24

(Japan - no data)

No of patient on renal replacement therapy 7160 ( 1025 pmp)

Hong Kong Renal Registry香港醫院管理局腎病註冊1998rarr2008 uarr 19 times

The reasons of this growth are

ndash Global ageing

ndash Multi-morbid population

ndash Higher life-expectancy of ESRD patients

ndash Increasing access of younger people in countries in which RRT has been limited until today

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Lung Cancer

KidneyFailure

ColonCancer

BreastCancer

Prostate Cancer

57

99

4232

Kidney Failure Compared to Cancer Deaths in the US in 2000

(in Thousands)157

SEER 2003(Surveillance Epidemiology and End Results)

1200

600

0

Ten

year

med

ical

cos

ts o

f di

alys

is p

opul

atio

n$

( bill

ions

)

1981-1990 1991-2000 2001-2010

800

1000

$

$

$

PREDICTED DIALYSIS COST OF APPROXIMATELY $ 11 TRILLION$ 11 TRILLION FOR THE COMING DECADE

400

200

Lysaght MJ J Am Soc Nephrol 2002 13 S37-40

De Vecchi AF et al NDT 1999

Dialysis Cost Europe

25 - 38 times gt National Average

Prevalence of ESRD in 2004 versus economic welfare in the 75 Prevalence of ESRD in 2004 versus economic welfare in the 75 countries with the largest ESRD patient populationscountries with the largest ESRD patient populations

Grassmann A et al Nephrol Dial Transplant 2005 202587-2593

Regional ESRD distributionRegion Pop GDP ESRD

million US$ (000) Prevalence pmp

EU 380 217 790Europe 804 120 393M East 271 32 150Africa 833 10 55LAmerica 512 38 310Asia 3316 11 55Japan 127 376 1830NAmerica 310 295 1400

Moeller S et al Nephrol Dial Transplant 2002 Dec17(12)2071-6

Morelinkage

withGDP

than the general

population

China Future Dialysis Expense

￥0

￥5

￥10

￥15

￥20

￥25

￥30

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Bill

ions

Ann

ual E

xpen

ditu

re o

n D

ialy

sis

￥7143670260

￥29087632671Factors98 dialysis population growth per yearModality share remains 90 HD 10 PD

Source amp Courtesy CMIA 2006 data

(From 71 billion in 2005 to 29 billion in 2020)

TIME December 8 2003Newsweek Sept 4 2000

Percentage of incident patients

with diabetes 2006

data presented only for those countries from which relevant information was available All rates are unadjusted ^UK England Wales amp Northern Ireland (Scotland data reported separately) Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only Latest data for Canada Croatia amp Italy are for 2005 Data for France include 13 regions in 2005 amp 15 regions in 2006

1 Malaysia 5752 Mexico 4993 USA 4434 Japan 4255 Taiwan 424

8 Hong Kong 41

18 Australia 324

USRDS 2008

Diagnosis Distribution of NEW patients 2006 - 2007GN

217

Obstructive28

Unknown179

DM393

Others38

HTvascular106

Inherited cong30

Infection reflux08

新症病人之病因 (2006-7)

感染

遺傳

尿道阻塞

高血壓糖尿病

腎小球腎炎

DM 393

GN 217

Hong Kong Renal Registry香港醫院管理局腎病註冊

World

20002030

154 m370 m

55 m84 m

Developed Developing

99 m286 m

167338

329

182

524307

28391

809

228

423

186

09 16

20002030

In million subjects

102

81

71

211

255

127

78

THE GLOBAL BURDEN OF DIABETES (2000-2030)

WHO March 2003

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Consensus Workshop

Part 1 Detection of chronic kidney disease

Part 2 Evaluation and estimating progression of chronic kidney disease

Part 3 Measures to prevent the progression of chronic kidney disease

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)s2-7

Summary of the Consensus Statements (1)Summary of the Consensus Statements (1)

bull It is recommended to establish a global surveillance center (ISN Kidney Disease Data Centre or ISN KDDC) to coordinate worldwide standardized screening studies with standardized screening techniques in appropriate target groups to allow for the collection of clearly comparable data

bull It is recommended that patients diagnosed with diabetes and hypertension

should have regular screening for development of kidney disease

bull It is recommended that close relatives of patients with nephropathy due to diabetes hypertension and glomerulonephritis should also be the primary targets for screening to detect clinically silent kidney disease

bull No consensus was made on an exact age ldquocut-offrdquo for initiating CKD screening

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

SHAREScreening for Hong Kong Asymptomatic Renal

Population and Evaluation programme

普查計劃

腎康體健

Li PKT et al Kidney Int 2005 Apr(94)s36-40

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

China ESRD Growth Rate To Exceed That of Population

1150000000

1200000000

1250000000

1300000000

1350000000

1400000000

1450000000

1500000000

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Tota

l Pop

ulat

ion

0

50000

100000

150000

200000

250000

300000

350000

ESR

D P

atie

nts

Population Dialysis patients

ACTUAL PROJECTED

ESRD Patients07 per year

~10-12 per year

Population

Source amp CourtesyCMIA 2006 data

Incidence of ESRF (for 12 months ending 31032007) 1074 (164 pmp)

641697

789 798 830885

1019 1012960

1045 1040 1074

0100200300400500600700800900

100011001200

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

Incidence of ESRF on RRT

Hong Kong Renal Registry香港醫院管理局腎病註冊

Incidence of ESRD (pmp) by age 2005

USRDS 2007

0-19 20-44 45-64 65-74 gt75

No14 No 4 No 5 No 8 No 24

(Japan - no data)

No of patient on renal replacement therapy 7160 ( 1025 pmp)

Hong Kong Renal Registry香港醫院管理局腎病註冊1998rarr2008 uarr 19 times

The reasons of this growth are

ndash Global ageing

ndash Multi-morbid population

ndash Higher life-expectancy of ESRD patients

ndash Increasing access of younger people in countries in which RRT has been limited until today

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Lung Cancer

KidneyFailure

ColonCancer

BreastCancer

Prostate Cancer

57

99

4232

Kidney Failure Compared to Cancer Deaths in the US in 2000

(in Thousands)157

SEER 2003(Surveillance Epidemiology and End Results)

1200

600

0

Ten

year

med

ical

cos

ts o

f di

alys

is p

opul

atio

n$

( bill

ions

)

1981-1990 1991-2000 2001-2010

800

1000

$

$

$

PREDICTED DIALYSIS COST OF APPROXIMATELY $ 11 TRILLION$ 11 TRILLION FOR THE COMING DECADE

400

200

Lysaght MJ J Am Soc Nephrol 2002 13 S37-40

De Vecchi AF et al NDT 1999

Dialysis Cost Europe

25 - 38 times gt National Average

Prevalence of ESRD in 2004 versus economic welfare in the 75 Prevalence of ESRD in 2004 versus economic welfare in the 75 countries with the largest ESRD patient populationscountries with the largest ESRD patient populations

Grassmann A et al Nephrol Dial Transplant 2005 202587-2593

Regional ESRD distributionRegion Pop GDP ESRD

million US$ (000) Prevalence pmp

EU 380 217 790Europe 804 120 393M East 271 32 150Africa 833 10 55LAmerica 512 38 310Asia 3316 11 55Japan 127 376 1830NAmerica 310 295 1400

Moeller S et al Nephrol Dial Transplant 2002 Dec17(12)2071-6

Morelinkage

withGDP

than the general

population

China Future Dialysis Expense

￥0

￥5

￥10

￥15

￥20

￥25

￥30

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Bill

ions

Ann

ual E

xpen

ditu

re o

n D

ialy

sis

￥7143670260

￥29087632671Factors98 dialysis population growth per yearModality share remains 90 HD 10 PD

Source amp Courtesy CMIA 2006 data

(From 71 billion in 2005 to 29 billion in 2020)

TIME December 8 2003Newsweek Sept 4 2000

Percentage of incident patients

with diabetes 2006

data presented only for those countries from which relevant information was available All rates are unadjusted ^UK England Wales amp Northern Ireland (Scotland data reported separately) Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only Latest data for Canada Croatia amp Italy are for 2005 Data for France include 13 regions in 2005 amp 15 regions in 2006

1 Malaysia 5752 Mexico 4993 USA 4434 Japan 4255 Taiwan 424

8 Hong Kong 41

18 Australia 324

USRDS 2008

Diagnosis Distribution of NEW patients 2006 - 2007GN

217

Obstructive28

Unknown179

DM393

Others38

HTvascular106

Inherited cong30

Infection reflux08

新症病人之病因 (2006-7)

感染

遺傳

尿道阻塞

高血壓糖尿病

腎小球腎炎

DM 393

GN 217

Hong Kong Renal Registry香港醫院管理局腎病註冊

World

20002030

154 m370 m

55 m84 m

Developed Developing

99 m286 m

167338

329

182

524307

28391

809

228

423

186

09 16

20002030

In million subjects

102

81

71

211

255

127

78

THE GLOBAL BURDEN OF DIABETES (2000-2030)

WHO March 2003

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Consensus Workshop

Part 1 Detection of chronic kidney disease

Part 2 Evaluation and estimating progression of chronic kidney disease

Part 3 Measures to prevent the progression of chronic kidney disease

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)s2-7

Summary of the Consensus Statements (1)Summary of the Consensus Statements (1)

bull It is recommended to establish a global surveillance center (ISN Kidney Disease Data Centre or ISN KDDC) to coordinate worldwide standardized screening studies with standardized screening techniques in appropriate target groups to allow for the collection of clearly comparable data

bull It is recommended that patients diagnosed with diabetes and hypertension

should have regular screening for development of kidney disease

bull It is recommended that close relatives of patients with nephropathy due to diabetes hypertension and glomerulonephritis should also be the primary targets for screening to detect clinically silent kidney disease

bull No consensus was made on an exact age ldquocut-offrdquo for initiating CKD screening

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

SHAREScreening for Hong Kong Asymptomatic Renal

Population and Evaluation programme

普查計劃

腎康體健

Li PKT et al Kidney Int 2005 Apr(94)s36-40

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Incidence of ESRF (for 12 months ending 31032007) 1074 (164 pmp)

641697

789 798 830885

1019 1012960

1045 1040 1074

0100200300400500600700800900

100011001200

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

Incidence of ESRF on RRT

Hong Kong Renal Registry香港醫院管理局腎病註冊

Incidence of ESRD (pmp) by age 2005

USRDS 2007

0-19 20-44 45-64 65-74 gt75

No14 No 4 No 5 No 8 No 24

(Japan - no data)

No of patient on renal replacement therapy 7160 ( 1025 pmp)

Hong Kong Renal Registry香港醫院管理局腎病註冊1998rarr2008 uarr 19 times

The reasons of this growth are

ndash Global ageing

ndash Multi-morbid population

ndash Higher life-expectancy of ESRD patients

ndash Increasing access of younger people in countries in which RRT has been limited until today

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Lung Cancer

KidneyFailure

ColonCancer

BreastCancer

Prostate Cancer

57

99

4232

Kidney Failure Compared to Cancer Deaths in the US in 2000

(in Thousands)157

SEER 2003(Surveillance Epidemiology and End Results)

1200

600

0

Ten

year

med

ical

cos

ts o

f di

alys

is p

opul

atio

n$

( bill

ions

)

1981-1990 1991-2000 2001-2010

800

1000

$

$

$

PREDICTED DIALYSIS COST OF APPROXIMATELY $ 11 TRILLION$ 11 TRILLION FOR THE COMING DECADE

400

200

Lysaght MJ J Am Soc Nephrol 2002 13 S37-40

De Vecchi AF et al NDT 1999

Dialysis Cost Europe

25 - 38 times gt National Average

Prevalence of ESRD in 2004 versus economic welfare in the 75 Prevalence of ESRD in 2004 versus economic welfare in the 75 countries with the largest ESRD patient populationscountries with the largest ESRD patient populations

Grassmann A et al Nephrol Dial Transplant 2005 202587-2593

Regional ESRD distributionRegion Pop GDP ESRD

million US$ (000) Prevalence pmp

EU 380 217 790Europe 804 120 393M East 271 32 150Africa 833 10 55LAmerica 512 38 310Asia 3316 11 55Japan 127 376 1830NAmerica 310 295 1400

Moeller S et al Nephrol Dial Transplant 2002 Dec17(12)2071-6

Morelinkage

withGDP

than the general

population

China Future Dialysis Expense

￥0

￥5

￥10

￥15

￥20

￥25

￥30

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Bill

ions

Ann

ual E

xpen

ditu

re o

n D

ialy

sis

￥7143670260

￥29087632671Factors98 dialysis population growth per yearModality share remains 90 HD 10 PD

Source amp Courtesy CMIA 2006 data

(From 71 billion in 2005 to 29 billion in 2020)

TIME December 8 2003Newsweek Sept 4 2000

Percentage of incident patients

with diabetes 2006

data presented only for those countries from which relevant information was available All rates are unadjusted ^UK England Wales amp Northern Ireland (Scotland data reported separately) Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only Latest data for Canada Croatia amp Italy are for 2005 Data for France include 13 regions in 2005 amp 15 regions in 2006

1 Malaysia 5752 Mexico 4993 USA 4434 Japan 4255 Taiwan 424

8 Hong Kong 41

18 Australia 324

USRDS 2008

Diagnosis Distribution of NEW patients 2006 - 2007GN

217

Obstructive28

Unknown179

DM393

Others38

HTvascular106

Inherited cong30

Infection reflux08

新症病人之病因 (2006-7)

感染

遺傳

尿道阻塞

高血壓糖尿病

腎小球腎炎

DM 393

GN 217

Hong Kong Renal Registry香港醫院管理局腎病註冊

World

20002030

154 m370 m

55 m84 m

Developed Developing

99 m286 m

167338

329

182

524307

28391

809

228

423

186

09 16

20002030

In million subjects

102

81

71

211

255

127

78

THE GLOBAL BURDEN OF DIABETES (2000-2030)

WHO March 2003

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Consensus Workshop

Part 1 Detection of chronic kidney disease

Part 2 Evaluation and estimating progression of chronic kidney disease

Part 3 Measures to prevent the progression of chronic kidney disease

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)s2-7

Summary of the Consensus Statements (1)Summary of the Consensus Statements (1)

bull It is recommended to establish a global surveillance center (ISN Kidney Disease Data Centre or ISN KDDC) to coordinate worldwide standardized screening studies with standardized screening techniques in appropriate target groups to allow for the collection of clearly comparable data

bull It is recommended that patients diagnosed with diabetes and hypertension

should have regular screening for development of kidney disease

bull It is recommended that close relatives of patients with nephropathy due to diabetes hypertension and glomerulonephritis should also be the primary targets for screening to detect clinically silent kidney disease

bull No consensus was made on an exact age ldquocut-offrdquo for initiating CKD screening

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

SHAREScreening for Hong Kong Asymptomatic Renal

Population and Evaluation programme

普查計劃

腎康體健

Li PKT et al Kidney Int 2005 Apr(94)s36-40

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Incidence of ESRD (pmp) by age 2005

USRDS 2007

0-19 20-44 45-64 65-74 gt75

No14 No 4 No 5 No 8 No 24

(Japan - no data)

No of patient on renal replacement therapy 7160 ( 1025 pmp)

Hong Kong Renal Registry香港醫院管理局腎病註冊1998rarr2008 uarr 19 times

The reasons of this growth are

ndash Global ageing

ndash Multi-morbid population

ndash Higher life-expectancy of ESRD patients

ndash Increasing access of younger people in countries in which RRT has been limited until today

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Lung Cancer

KidneyFailure

ColonCancer

BreastCancer

Prostate Cancer

57

99

4232

Kidney Failure Compared to Cancer Deaths in the US in 2000

(in Thousands)157

SEER 2003(Surveillance Epidemiology and End Results)

1200

600

0

Ten

year

med

ical

cos

ts o

f di

alys

is p

opul

atio

n$

( bill

ions

)

1981-1990 1991-2000 2001-2010

800

1000

$

$

$

PREDICTED DIALYSIS COST OF APPROXIMATELY $ 11 TRILLION$ 11 TRILLION FOR THE COMING DECADE

400

200

Lysaght MJ J Am Soc Nephrol 2002 13 S37-40

De Vecchi AF et al NDT 1999

Dialysis Cost Europe

25 - 38 times gt National Average

Prevalence of ESRD in 2004 versus economic welfare in the 75 Prevalence of ESRD in 2004 versus economic welfare in the 75 countries with the largest ESRD patient populationscountries with the largest ESRD patient populations

Grassmann A et al Nephrol Dial Transplant 2005 202587-2593

Regional ESRD distributionRegion Pop GDP ESRD

million US$ (000) Prevalence pmp

EU 380 217 790Europe 804 120 393M East 271 32 150Africa 833 10 55LAmerica 512 38 310Asia 3316 11 55Japan 127 376 1830NAmerica 310 295 1400

Moeller S et al Nephrol Dial Transplant 2002 Dec17(12)2071-6

Morelinkage

withGDP

than the general

population

China Future Dialysis Expense

￥0

￥5

￥10

￥15

￥20

￥25

￥30

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Bill

ions

Ann

ual E

xpen

ditu

re o

n D

ialy

sis

￥7143670260

￥29087632671Factors98 dialysis population growth per yearModality share remains 90 HD 10 PD

Source amp Courtesy CMIA 2006 data

(From 71 billion in 2005 to 29 billion in 2020)

TIME December 8 2003Newsweek Sept 4 2000

Percentage of incident patients

with diabetes 2006

data presented only for those countries from which relevant information was available All rates are unadjusted ^UK England Wales amp Northern Ireland (Scotland data reported separately) Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only Latest data for Canada Croatia amp Italy are for 2005 Data for France include 13 regions in 2005 amp 15 regions in 2006

1 Malaysia 5752 Mexico 4993 USA 4434 Japan 4255 Taiwan 424

8 Hong Kong 41

18 Australia 324

USRDS 2008

Diagnosis Distribution of NEW patients 2006 - 2007GN

217

Obstructive28

Unknown179

DM393

Others38

HTvascular106

Inherited cong30

Infection reflux08

新症病人之病因 (2006-7)

感染

遺傳

尿道阻塞

高血壓糖尿病

腎小球腎炎

DM 393

GN 217

Hong Kong Renal Registry香港醫院管理局腎病註冊

World

20002030

154 m370 m

55 m84 m

Developed Developing

99 m286 m

167338

329

182

524307

28391

809

228

423

186

09 16

20002030

In million subjects

102

81

71

211

255

127

78

THE GLOBAL BURDEN OF DIABETES (2000-2030)

WHO March 2003

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Consensus Workshop

Part 1 Detection of chronic kidney disease

Part 2 Evaluation and estimating progression of chronic kidney disease

Part 3 Measures to prevent the progression of chronic kidney disease

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)s2-7

Summary of the Consensus Statements (1)Summary of the Consensus Statements (1)

bull It is recommended to establish a global surveillance center (ISN Kidney Disease Data Centre or ISN KDDC) to coordinate worldwide standardized screening studies with standardized screening techniques in appropriate target groups to allow for the collection of clearly comparable data

bull It is recommended that patients diagnosed with diabetes and hypertension

should have regular screening for development of kidney disease

bull It is recommended that close relatives of patients with nephropathy due to diabetes hypertension and glomerulonephritis should also be the primary targets for screening to detect clinically silent kidney disease

bull No consensus was made on an exact age ldquocut-offrdquo for initiating CKD screening

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

SHAREScreening for Hong Kong Asymptomatic Renal

Population and Evaluation programme

普查計劃

腎康體健

Li PKT et al Kidney Int 2005 Apr(94)s36-40

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

No of patient on renal replacement therapy 7160 ( 1025 pmp)

Hong Kong Renal Registry香港醫院管理局腎病註冊1998rarr2008 uarr 19 times

The reasons of this growth are

ndash Global ageing

ndash Multi-morbid population

ndash Higher life-expectancy of ESRD patients

ndash Increasing access of younger people in countries in which RRT has been limited until today

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Lung Cancer

KidneyFailure

ColonCancer

BreastCancer

Prostate Cancer

57

99

4232

Kidney Failure Compared to Cancer Deaths in the US in 2000

(in Thousands)157

SEER 2003(Surveillance Epidemiology and End Results)

1200

600

0

Ten

year

med

ical

cos

ts o

f di

alys

is p

opul

atio

n$

( bill

ions

)

1981-1990 1991-2000 2001-2010

800

1000

$

$

$

PREDICTED DIALYSIS COST OF APPROXIMATELY $ 11 TRILLION$ 11 TRILLION FOR THE COMING DECADE

400

200

Lysaght MJ J Am Soc Nephrol 2002 13 S37-40

De Vecchi AF et al NDT 1999

Dialysis Cost Europe

25 - 38 times gt National Average

Prevalence of ESRD in 2004 versus economic welfare in the 75 Prevalence of ESRD in 2004 versus economic welfare in the 75 countries with the largest ESRD patient populationscountries with the largest ESRD patient populations

Grassmann A et al Nephrol Dial Transplant 2005 202587-2593

Regional ESRD distributionRegion Pop GDP ESRD

million US$ (000) Prevalence pmp

EU 380 217 790Europe 804 120 393M East 271 32 150Africa 833 10 55LAmerica 512 38 310Asia 3316 11 55Japan 127 376 1830NAmerica 310 295 1400

Moeller S et al Nephrol Dial Transplant 2002 Dec17(12)2071-6

Morelinkage

withGDP

than the general

population

China Future Dialysis Expense

￥0

￥5

￥10

￥15

￥20

￥25

￥30

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Bill

ions

Ann

ual E

xpen

ditu

re o

n D

ialy

sis

￥7143670260

￥29087632671Factors98 dialysis population growth per yearModality share remains 90 HD 10 PD

Source amp Courtesy CMIA 2006 data

(From 71 billion in 2005 to 29 billion in 2020)

TIME December 8 2003Newsweek Sept 4 2000

Percentage of incident patients

with diabetes 2006

data presented only for those countries from which relevant information was available All rates are unadjusted ^UK England Wales amp Northern Ireland (Scotland data reported separately) Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only Latest data for Canada Croatia amp Italy are for 2005 Data for France include 13 regions in 2005 amp 15 regions in 2006

1 Malaysia 5752 Mexico 4993 USA 4434 Japan 4255 Taiwan 424

8 Hong Kong 41

18 Australia 324

USRDS 2008

Diagnosis Distribution of NEW patients 2006 - 2007GN

217

Obstructive28

Unknown179

DM393

Others38

HTvascular106

Inherited cong30

Infection reflux08

新症病人之病因 (2006-7)

感染

遺傳

尿道阻塞

高血壓糖尿病

腎小球腎炎

DM 393

GN 217

Hong Kong Renal Registry香港醫院管理局腎病註冊

World

20002030

154 m370 m

55 m84 m

Developed Developing

99 m286 m

167338

329

182

524307

28391

809

228

423

186

09 16

20002030

In million subjects

102

81

71

211

255

127

78

THE GLOBAL BURDEN OF DIABETES (2000-2030)

WHO March 2003

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Consensus Workshop

Part 1 Detection of chronic kidney disease

Part 2 Evaluation and estimating progression of chronic kidney disease

Part 3 Measures to prevent the progression of chronic kidney disease

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)s2-7

Summary of the Consensus Statements (1)Summary of the Consensus Statements (1)

bull It is recommended to establish a global surveillance center (ISN Kidney Disease Data Centre or ISN KDDC) to coordinate worldwide standardized screening studies with standardized screening techniques in appropriate target groups to allow for the collection of clearly comparable data

bull It is recommended that patients diagnosed with diabetes and hypertension

should have regular screening for development of kidney disease

bull It is recommended that close relatives of patients with nephropathy due to diabetes hypertension and glomerulonephritis should also be the primary targets for screening to detect clinically silent kidney disease

bull No consensus was made on an exact age ldquocut-offrdquo for initiating CKD screening

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

SHAREScreening for Hong Kong Asymptomatic Renal

Population and Evaluation programme

普查計劃

腎康體健

Li PKT et al Kidney Int 2005 Apr(94)s36-40

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The reasons of this growth are

ndash Global ageing

ndash Multi-morbid population

ndash Higher life-expectancy of ESRD patients

ndash Increasing access of younger people in countries in which RRT has been limited until today

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Lung Cancer

KidneyFailure

ColonCancer

BreastCancer

Prostate Cancer

57

99

4232

Kidney Failure Compared to Cancer Deaths in the US in 2000

(in Thousands)157

SEER 2003(Surveillance Epidemiology and End Results)

1200

600

0

Ten

year

med

ical

cos

ts o

f di

alys

is p

opul

atio

n$

( bill

ions

)

1981-1990 1991-2000 2001-2010

800

1000

$

$

$

PREDICTED DIALYSIS COST OF APPROXIMATELY $ 11 TRILLION$ 11 TRILLION FOR THE COMING DECADE

400

200

Lysaght MJ J Am Soc Nephrol 2002 13 S37-40

De Vecchi AF et al NDT 1999

Dialysis Cost Europe

25 - 38 times gt National Average

Prevalence of ESRD in 2004 versus economic welfare in the 75 Prevalence of ESRD in 2004 versus economic welfare in the 75 countries with the largest ESRD patient populationscountries with the largest ESRD patient populations

Grassmann A et al Nephrol Dial Transplant 2005 202587-2593

Regional ESRD distributionRegion Pop GDP ESRD

million US$ (000) Prevalence pmp

EU 380 217 790Europe 804 120 393M East 271 32 150Africa 833 10 55LAmerica 512 38 310Asia 3316 11 55Japan 127 376 1830NAmerica 310 295 1400

Moeller S et al Nephrol Dial Transplant 2002 Dec17(12)2071-6

Morelinkage

withGDP

than the general

population

China Future Dialysis Expense

￥0

￥5

￥10

￥15

￥20

￥25

￥30

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Bill

ions

Ann

ual E

xpen

ditu

re o

n D

ialy

sis

￥7143670260

￥29087632671Factors98 dialysis population growth per yearModality share remains 90 HD 10 PD

Source amp Courtesy CMIA 2006 data

(From 71 billion in 2005 to 29 billion in 2020)

TIME December 8 2003Newsweek Sept 4 2000

Percentage of incident patients

with diabetes 2006

data presented only for those countries from which relevant information was available All rates are unadjusted ^UK England Wales amp Northern Ireland (Scotland data reported separately) Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only Latest data for Canada Croatia amp Italy are for 2005 Data for France include 13 regions in 2005 amp 15 regions in 2006

1 Malaysia 5752 Mexico 4993 USA 4434 Japan 4255 Taiwan 424

8 Hong Kong 41

18 Australia 324

USRDS 2008

Diagnosis Distribution of NEW patients 2006 - 2007GN

217

Obstructive28

Unknown179

DM393

Others38

HTvascular106

Inherited cong30

Infection reflux08

新症病人之病因 (2006-7)

感染

遺傳

尿道阻塞

高血壓糖尿病

腎小球腎炎

DM 393

GN 217

Hong Kong Renal Registry香港醫院管理局腎病註冊

World

20002030

154 m370 m

55 m84 m

Developed Developing

99 m286 m

167338

329

182

524307

28391

809

228

423

186

09 16

20002030

In million subjects

102

81

71

211

255

127

78

THE GLOBAL BURDEN OF DIABETES (2000-2030)

WHO March 2003

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Consensus Workshop

Part 1 Detection of chronic kidney disease

Part 2 Evaluation and estimating progression of chronic kidney disease

Part 3 Measures to prevent the progression of chronic kidney disease

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)s2-7

Summary of the Consensus Statements (1)Summary of the Consensus Statements (1)

bull It is recommended to establish a global surveillance center (ISN Kidney Disease Data Centre or ISN KDDC) to coordinate worldwide standardized screening studies with standardized screening techniques in appropriate target groups to allow for the collection of clearly comparable data

bull It is recommended that patients diagnosed with diabetes and hypertension

should have regular screening for development of kidney disease

bull It is recommended that close relatives of patients with nephropathy due to diabetes hypertension and glomerulonephritis should also be the primary targets for screening to detect clinically silent kidney disease

bull No consensus was made on an exact age ldquocut-offrdquo for initiating CKD screening

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

SHAREScreening for Hong Kong Asymptomatic Renal

Population and Evaluation programme

普查計劃

腎康體健

Li PKT et al Kidney Int 2005 Apr(94)s36-40

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Lung Cancer

KidneyFailure

ColonCancer

BreastCancer

Prostate Cancer

57

99

4232

Kidney Failure Compared to Cancer Deaths in the US in 2000

(in Thousands)157

SEER 2003(Surveillance Epidemiology and End Results)

1200

600

0

Ten

year

med

ical

cos

ts o

f di

alys

is p

opul

atio

n$

( bill

ions

)

1981-1990 1991-2000 2001-2010

800

1000

$

$

$

PREDICTED DIALYSIS COST OF APPROXIMATELY $ 11 TRILLION$ 11 TRILLION FOR THE COMING DECADE

400

200

Lysaght MJ J Am Soc Nephrol 2002 13 S37-40

De Vecchi AF et al NDT 1999

Dialysis Cost Europe

25 - 38 times gt National Average

Prevalence of ESRD in 2004 versus economic welfare in the 75 Prevalence of ESRD in 2004 versus economic welfare in the 75 countries with the largest ESRD patient populationscountries with the largest ESRD patient populations

Grassmann A et al Nephrol Dial Transplant 2005 202587-2593

Regional ESRD distributionRegion Pop GDP ESRD

million US$ (000) Prevalence pmp

EU 380 217 790Europe 804 120 393M East 271 32 150Africa 833 10 55LAmerica 512 38 310Asia 3316 11 55Japan 127 376 1830NAmerica 310 295 1400

Moeller S et al Nephrol Dial Transplant 2002 Dec17(12)2071-6

Morelinkage

withGDP

than the general

population

China Future Dialysis Expense

￥0

￥5

￥10

￥15

￥20

￥25

￥30

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Bill

ions

Ann

ual E

xpen

ditu

re o

n D

ialy

sis

￥7143670260

￥29087632671Factors98 dialysis population growth per yearModality share remains 90 HD 10 PD

Source amp Courtesy CMIA 2006 data

(From 71 billion in 2005 to 29 billion in 2020)

TIME December 8 2003Newsweek Sept 4 2000

Percentage of incident patients

with diabetes 2006

data presented only for those countries from which relevant information was available All rates are unadjusted ^UK England Wales amp Northern Ireland (Scotland data reported separately) Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only Latest data for Canada Croatia amp Italy are for 2005 Data for France include 13 regions in 2005 amp 15 regions in 2006

1 Malaysia 5752 Mexico 4993 USA 4434 Japan 4255 Taiwan 424

8 Hong Kong 41

18 Australia 324

USRDS 2008

Diagnosis Distribution of NEW patients 2006 - 2007GN

217

Obstructive28

Unknown179

DM393

Others38

HTvascular106

Inherited cong30

Infection reflux08

新症病人之病因 (2006-7)

感染

遺傳

尿道阻塞

高血壓糖尿病

腎小球腎炎

DM 393

GN 217

Hong Kong Renal Registry香港醫院管理局腎病註冊

World

20002030

154 m370 m

55 m84 m

Developed Developing

99 m286 m

167338

329

182

524307

28391

809

228

423

186

09 16

20002030

In million subjects

102

81

71

211

255

127

78

THE GLOBAL BURDEN OF DIABETES (2000-2030)

WHO March 2003

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Consensus Workshop

Part 1 Detection of chronic kidney disease

Part 2 Evaluation and estimating progression of chronic kidney disease

Part 3 Measures to prevent the progression of chronic kidney disease

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)s2-7

Summary of the Consensus Statements (1)Summary of the Consensus Statements (1)

bull It is recommended to establish a global surveillance center (ISN Kidney Disease Data Centre or ISN KDDC) to coordinate worldwide standardized screening studies with standardized screening techniques in appropriate target groups to allow for the collection of clearly comparable data

bull It is recommended that patients diagnosed with diabetes and hypertension

should have regular screening for development of kidney disease

bull It is recommended that close relatives of patients with nephropathy due to diabetes hypertension and glomerulonephritis should also be the primary targets for screening to detect clinically silent kidney disease

bull No consensus was made on an exact age ldquocut-offrdquo for initiating CKD screening

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

SHAREScreening for Hong Kong Asymptomatic Renal

Population and Evaluation programme

普查計劃

腎康體健

Li PKT et al Kidney Int 2005 Apr(94)s36-40

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Lung Cancer

KidneyFailure

ColonCancer

BreastCancer

Prostate Cancer

57

99

4232

Kidney Failure Compared to Cancer Deaths in the US in 2000

(in Thousands)157

SEER 2003(Surveillance Epidemiology and End Results)

1200

600

0

Ten

year

med

ical

cos

ts o

f di

alys

is p

opul

atio

n$

( bill

ions

)

1981-1990 1991-2000 2001-2010

800

1000

$

$

$

PREDICTED DIALYSIS COST OF APPROXIMATELY $ 11 TRILLION$ 11 TRILLION FOR THE COMING DECADE

400

200

Lysaght MJ J Am Soc Nephrol 2002 13 S37-40

De Vecchi AF et al NDT 1999

Dialysis Cost Europe

25 - 38 times gt National Average

Prevalence of ESRD in 2004 versus economic welfare in the 75 Prevalence of ESRD in 2004 versus economic welfare in the 75 countries with the largest ESRD patient populationscountries with the largest ESRD patient populations

Grassmann A et al Nephrol Dial Transplant 2005 202587-2593

Regional ESRD distributionRegion Pop GDP ESRD

million US$ (000) Prevalence pmp

EU 380 217 790Europe 804 120 393M East 271 32 150Africa 833 10 55LAmerica 512 38 310Asia 3316 11 55Japan 127 376 1830NAmerica 310 295 1400

Moeller S et al Nephrol Dial Transplant 2002 Dec17(12)2071-6

Morelinkage

withGDP

than the general

population

China Future Dialysis Expense

￥0

￥5

￥10

￥15

￥20

￥25

￥30

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Bill

ions

Ann

ual E

xpen

ditu

re o

n D

ialy

sis

￥7143670260

￥29087632671Factors98 dialysis population growth per yearModality share remains 90 HD 10 PD

Source amp Courtesy CMIA 2006 data

(From 71 billion in 2005 to 29 billion in 2020)

TIME December 8 2003Newsweek Sept 4 2000

Percentage of incident patients

with diabetes 2006

data presented only for those countries from which relevant information was available All rates are unadjusted ^UK England Wales amp Northern Ireland (Scotland data reported separately) Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only Latest data for Canada Croatia amp Italy are for 2005 Data for France include 13 regions in 2005 amp 15 regions in 2006

1 Malaysia 5752 Mexico 4993 USA 4434 Japan 4255 Taiwan 424

8 Hong Kong 41

18 Australia 324

USRDS 2008

Diagnosis Distribution of NEW patients 2006 - 2007GN

217

Obstructive28

Unknown179

DM393

Others38

HTvascular106

Inherited cong30

Infection reflux08

新症病人之病因 (2006-7)

感染

遺傳

尿道阻塞

高血壓糖尿病

腎小球腎炎

DM 393

GN 217

Hong Kong Renal Registry香港醫院管理局腎病註冊

World

20002030

154 m370 m

55 m84 m

Developed Developing

99 m286 m

167338

329

182

524307

28391

809

228

423

186

09 16

20002030

In million subjects

102

81

71

211

255

127

78

THE GLOBAL BURDEN OF DIABETES (2000-2030)

WHO March 2003

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Consensus Workshop

Part 1 Detection of chronic kidney disease

Part 2 Evaluation and estimating progression of chronic kidney disease

Part 3 Measures to prevent the progression of chronic kidney disease

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)s2-7

Summary of the Consensus Statements (1)Summary of the Consensus Statements (1)

bull It is recommended to establish a global surveillance center (ISN Kidney Disease Data Centre or ISN KDDC) to coordinate worldwide standardized screening studies with standardized screening techniques in appropriate target groups to allow for the collection of clearly comparable data

bull It is recommended that patients diagnosed with diabetes and hypertension

should have regular screening for development of kidney disease

bull It is recommended that close relatives of patients with nephropathy due to diabetes hypertension and glomerulonephritis should also be the primary targets for screening to detect clinically silent kidney disease

bull No consensus was made on an exact age ldquocut-offrdquo for initiating CKD screening

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

SHAREScreening for Hong Kong Asymptomatic Renal

Population and Evaluation programme

普查計劃

腎康體健

Li PKT et al Kidney Int 2005 Apr(94)s36-40

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

1200

600

0

Ten

year

med

ical

cos

ts o

f di

alys

is p

opul

atio

n$

( bill

ions

)

1981-1990 1991-2000 2001-2010

800

1000

$

$

$

PREDICTED DIALYSIS COST OF APPROXIMATELY $ 11 TRILLION$ 11 TRILLION FOR THE COMING DECADE

400

200

Lysaght MJ J Am Soc Nephrol 2002 13 S37-40

De Vecchi AF et al NDT 1999

Dialysis Cost Europe

25 - 38 times gt National Average

Prevalence of ESRD in 2004 versus economic welfare in the 75 Prevalence of ESRD in 2004 versus economic welfare in the 75 countries with the largest ESRD patient populationscountries with the largest ESRD patient populations

Grassmann A et al Nephrol Dial Transplant 2005 202587-2593

Regional ESRD distributionRegion Pop GDP ESRD

million US$ (000) Prevalence pmp

EU 380 217 790Europe 804 120 393M East 271 32 150Africa 833 10 55LAmerica 512 38 310Asia 3316 11 55Japan 127 376 1830NAmerica 310 295 1400

Moeller S et al Nephrol Dial Transplant 2002 Dec17(12)2071-6

Morelinkage

withGDP

than the general

population

China Future Dialysis Expense

￥0

￥5

￥10

￥15

￥20

￥25

￥30

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Bill

ions

Ann

ual E

xpen

ditu

re o

n D

ialy

sis

￥7143670260

￥29087632671Factors98 dialysis population growth per yearModality share remains 90 HD 10 PD

Source amp Courtesy CMIA 2006 data

(From 71 billion in 2005 to 29 billion in 2020)

TIME December 8 2003Newsweek Sept 4 2000

Percentage of incident patients

with diabetes 2006

data presented only for those countries from which relevant information was available All rates are unadjusted ^UK England Wales amp Northern Ireland (Scotland data reported separately) Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only Latest data for Canada Croatia amp Italy are for 2005 Data for France include 13 regions in 2005 amp 15 regions in 2006

1 Malaysia 5752 Mexico 4993 USA 4434 Japan 4255 Taiwan 424

8 Hong Kong 41

18 Australia 324

USRDS 2008

Diagnosis Distribution of NEW patients 2006 - 2007GN

217

Obstructive28

Unknown179

DM393

Others38

HTvascular106

Inherited cong30

Infection reflux08

新症病人之病因 (2006-7)

感染

遺傳

尿道阻塞

高血壓糖尿病

腎小球腎炎

DM 393

GN 217

Hong Kong Renal Registry香港醫院管理局腎病註冊

World

20002030

154 m370 m

55 m84 m

Developed Developing

99 m286 m

167338

329

182

524307

28391

809

228

423

186

09 16

20002030

In million subjects

102

81

71

211

255

127

78

THE GLOBAL BURDEN OF DIABETES (2000-2030)

WHO March 2003

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Consensus Workshop

Part 1 Detection of chronic kidney disease

Part 2 Evaluation and estimating progression of chronic kidney disease

Part 3 Measures to prevent the progression of chronic kidney disease

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)s2-7

Summary of the Consensus Statements (1)Summary of the Consensus Statements (1)

bull It is recommended to establish a global surveillance center (ISN Kidney Disease Data Centre or ISN KDDC) to coordinate worldwide standardized screening studies with standardized screening techniques in appropriate target groups to allow for the collection of clearly comparable data

bull It is recommended that patients diagnosed with diabetes and hypertension

should have regular screening for development of kidney disease

bull It is recommended that close relatives of patients with nephropathy due to diabetes hypertension and glomerulonephritis should also be the primary targets for screening to detect clinically silent kidney disease

bull No consensus was made on an exact age ldquocut-offrdquo for initiating CKD screening

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

SHAREScreening for Hong Kong Asymptomatic Renal

Population and Evaluation programme

普查計劃

腎康體健

Li PKT et al Kidney Int 2005 Apr(94)s36-40

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

De Vecchi AF et al NDT 1999

Dialysis Cost Europe

25 - 38 times gt National Average

Prevalence of ESRD in 2004 versus economic welfare in the 75 Prevalence of ESRD in 2004 versus economic welfare in the 75 countries with the largest ESRD patient populationscountries with the largest ESRD patient populations

Grassmann A et al Nephrol Dial Transplant 2005 202587-2593

Regional ESRD distributionRegion Pop GDP ESRD

million US$ (000) Prevalence pmp

EU 380 217 790Europe 804 120 393M East 271 32 150Africa 833 10 55LAmerica 512 38 310Asia 3316 11 55Japan 127 376 1830NAmerica 310 295 1400

Moeller S et al Nephrol Dial Transplant 2002 Dec17(12)2071-6

Morelinkage

withGDP

than the general

population

China Future Dialysis Expense

￥0

￥5

￥10

￥15

￥20

￥25

￥30

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Bill

ions

Ann

ual E

xpen

ditu

re o

n D

ialy

sis

￥7143670260

￥29087632671Factors98 dialysis population growth per yearModality share remains 90 HD 10 PD

Source amp Courtesy CMIA 2006 data

(From 71 billion in 2005 to 29 billion in 2020)

TIME December 8 2003Newsweek Sept 4 2000

Percentage of incident patients

with diabetes 2006

data presented only for those countries from which relevant information was available All rates are unadjusted ^UK England Wales amp Northern Ireland (Scotland data reported separately) Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only Latest data for Canada Croatia amp Italy are for 2005 Data for France include 13 regions in 2005 amp 15 regions in 2006

1 Malaysia 5752 Mexico 4993 USA 4434 Japan 4255 Taiwan 424

8 Hong Kong 41

18 Australia 324

USRDS 2008

Diagnosis Distribution of NEW patients 2006 - 2007GN

217

Obstructive28

Unknown179

DM393

Others38

HTvascular106

Inherited cong30

Infection reflux08

新症病人之病因 (2006-7)

感染

遺傳

尿道阻塞

高血壓糖尿病

腎小球腎炎

DM 393

GN 217

Hong Kong Renal Registry香港醫院管理局腎病註冊

World

20002030

154 m370 m

55 m84 m

Developed Developing

99 m286 m

167338

329

182

524307

28391

809

228

423

186

09 16

20002030

In million subjects

102

81

71

211

255

127

78

THE GLOBAL BURDEN OF DIABETES (2000-2030)

WHO March 2003

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Consensus Workshop

Part 1 Detection of chronic kidney disease

Part 2 Evaluation and estimating progression of chronic kidney disease

Part 3 Measures to prevent the progression of chronic kidney disease

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)s2-7

Summary of the Consensus Statements (1)Summary of the Consensus Statements (1)

bull It is recommended to establish a global surveillance center (ISN Kidney Disease Data Centre or ISN KDDC) to coordinate worldwide standardized screening studies with standardized screening techniques in appropriate target groups to allow for the collection of clearly comparable data

bull It is recommended that patients diagnosed with diabetes and hypertension

should have regular screening for development of kidney disease

bull It is recommended that close relatives of patients with nephropathy due to diabetes hypertension and glomerulonephritis should also be the primary targets for screening to detect clinically silent kidney disease

bull No consensus was made on an exact age ldquocut-offrdquo for initiating CKD screening

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

SHAREScreening for Hong Kong Asymptomatic Renal

Population and Evaluation programme

普查計劃

腎康體健

Li PKT et al Kidney Int 2005 Apr(94)s36-40

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Prevalence of ESRD in 2004 versus economic welfare in the 75 Prevalence of ESRD in 2004 versus economic welfare in the 75 countries with the largest ESRD patient populationscountries with the largest ESRD patient populations

Grassmann A et al Nephrol Dial Transplant 2005 202587-2593

Regional ESRD distributionRegion Pop GDP ESRD

million US$ (000) Prevalence pmp

EU 380 217 790Europe 804 120 393M East 271 32 150Africa 833 10 55LAmerica 512 38 310Asia 3316 11 55Japan 127 376 1830NAmerica 310 295 1400

Moeller S et al Nephrol Dial Transplant 2002 Dec17(12)2071-6

Morelinkage

withGDP

than the general

population

China Future Dialysis Expense

￥0

￥5

￥10

￥15

￥20

￥25

￥30

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Bill

ions

Ann

ual E

xpen

ditu

re o

n D

ialy

sis

￥7143670260

￥29087632671Factors98 dialysis population growth per yearModality share remains 90 HD 10 PD

Source amp Courtesy CMIA 2006 data

(From 71 billion in 2005 to 29 billion in 2020)

TIME December 8 2003Newsweek Sept 4 2000

Percentage of incident patients

with diabetes 2006

data presented only for those countries from which relevant information was available All rates are unadjusted ^UK England Wales amp Northern Ireland (Scotland data reported separately) Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only Latest data for Canada Croatia amp Italy are for 2005 Data for France include 13 regions in 2005 amp 15 regions in 2006

1 Malaysia 5752 Mexico 4993 USA 4434 Japan 4255 Taiwan 424

8 Hong Kong 41

18 Australia 324

USRDS 2008

Diagnosis Distribution of NEW patients 2006 - 2007GN

217

Obstructive28

Unknown179

DM393

Others38

HTvascular106

Inherited cong30

Infection reflux08

新症病人之病因 (2006-7)

感染

遺傳

尿道阻塞

高血壓糖尿病

腎小球腎炎

DM 393

GN 217

Hong Kong Renal Registry香港醫院管理局腎病註冊

World

20002030

154 m370 m

55 m84 m

Developed Developing

99 m286 m

167338

329

182

524307

28391

809

228

423

186

09 16

20002030

In million subjects

102

81

71

211

255

127

78

THE GLOBAL BURDEN OF DIABETES (2000-2030)

WHO March 2003

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Consensus Workshop

Part 1 Detection of chronic kidney disease

Part 2 Evaluation and estimating progression of chronic kidney disease

Part 3 Measures to prevent the progression of chronic kidney disease

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)s2-7

Summary of the Consensus Statements (1)Summary of the Consensus Statements (1)

bull It is recommended to establish a global surveillance center (ISN Kidney Disease Data Centre or ISN KDDC) to coordinate worldwide standardized screening studies with standardized screening techniques in appropriate target groups to allow for the collection of clearly comparable data

bull It is recommended that patients diagnosed with diabetes and hypertension

should have regular screening for development of kidney disease

bull It is recommended that close relatives of patients with nephropathy due to diabetes hypertension and glomerulonephritis should also be the primary targets for screening to detect clinically silent kidney disease

bull No consensus was made on an exact age ldquocut-offrdquo for initiating CKD screening

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

SHAREScreening for Hong Kong Asymptomatic Renal

Population and Evaluation programme

普查計劃

腎康體健

Li PKT et al Kidney Int 2005 Apr(94)s36-40

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Regional ESRD distributionRegion Pop GDP ESRD

million US$ (000) Prevalence pmp

EU 380 217 790Europe 804 120 393M East 271 32 150Africa 833 10 55LAmerica 512 38 310Asia 3316 11 55Japan 127 376 1830NAmerica 310 295 1400

Moeller S et al Nephrol Dial Transplant 2002 Dec17(12)2071-6

Morelinkage

withGDP

than the general

population

China Future Dialysis Expense

￥0

￥5

￥10

￥15

￥20

￥25

￥30

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Bill

ions

Ann

ual E

xpen

ditu

re o

n D

ialy

sis

￥7143670260

￥29087632671Factors98 dialysis population growth per yearModality share remains 90 HD 10 PD

Source amp Courtesy CMIA 2006 data

(From 71 billion in 2005 to 29 billion in 2020)

TIME December 8 2003Newsweek Sept 4 2000

Percentage of incident patients

with diabetes 2006

data presented only for those countries from which relevant information was available All rates are unadjusted ^UK England Wales amp Northern Ireland (Scotland data reported separately) Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only Latest data for Canada Croatia amp Italy are for 2005 Data for France include 13 regions in 2005 amp 15 regions in 2006

1 Malaysia 5752 Mexico 4993 USA 4434 Japan 4255 Taiwan 424

8 Hong Kong 41

18 Australia 324

USRDS 2008

Diagnosis Distribution of NEW patients 2006 - 2007GN

217

Obstructive28

Unknown179

DM393

Others38

HTvascular106

Inherited cong30

Infection reflux08

新症病人之病因 (2006-7)

感染

遺傳

尿道阻塞

高血壓糖尿病

腎小球腎炎

DM 393

GN 217

Hong Kong Renal Registry香港醫院管理局腎病註冊

World

20002030

154 m370 m

55 m84 m

Developed Developing

99 m286 m

167338

329

182

524307

28391

809

228

423

186

09 16

20002030

In million subjects

102

81

71

211

255

127

78

THE GLOBAL BURDEN OF DIABETES (2000-2030)

WHO March 2003

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Consensus Workshop

Part 1 Detection of chronic kidney disease

Part 2 Evaluation and estimating progression of chronic kidney disease

Part 3 Measures to prevent the progression of chronic kidney disease

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)s2-7

Summary of the Consensus Statements (1)Summary of the Consensus Statements (1)

bull It is recommended to establish a global surveillance center (ISN Kidney Disease Data Centre or ISN KDDC) to coordinate worldwide standardized screening studies with standardized screening techniques in appropriate target groups to allow for the collection of clearly comparable data

bull It is recommended that patients diagnosed with diabetes and hypertension

should have regular screening for development of kidney disease

bull It is recommended that close relatives of patients with nephropathy due to diabetes hypertension and glomerulonephritis should also be the primary targets for screening to detect clinically silent kidney disease

bull No consensus was made on an exact age ldquocut-offrdquo for initiating CKD screening

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

SHAREScreening for Hong Kong Asymptomatic Renal

Population and Evaluation programme

普查計劃

腎康體健

Li PKT et al Kidney Int 2005 Apr(94)s36-40

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

China Future Dialysis Expense

￥0

￥5

￥10

￥15

￥20

￥25

￥30

2000

2002

2004

2006

2008

2010

2012

2014

2016

2018

2020

Bill

ions

Ann

ual E

xpen

ditu

re o

n D

ialy

sis

￥7143670260

￥29087632671Factors98 dialysis population growth per yearModality share remains 90 HD 10 PD

Source amp Courtesy CMIA 2006 data

(From 71 billion in 2005 to 29 billion in 2020)

TIME December 8 2003Newsweek Sept 4 2000

Percentage of incident patients

with diabetes 2006

data presented only for those countries from which relevant information was available All rates are unadjusted ^UK England Wales amp Northern Ireland (Scotland data reported separately) Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only Latest data for Canada Croatia amp Italy are for 2005 Data for France include 13 regions in 2005 amp 15 regions in 2006

1 Malaysia 5752 Mexico 4993 USA 4434 Japan 4255 Taiwan 424

8 Hong Kong 41

18 Australia 324

USRDS 2008

Diagnosis Distribution of NEW patients 2006 - 2007GN

217

Obstructive28

Unknown179

DM393

Others38

HTvascular106

Inherited cong30

Infection reflux08

新症病人之病因 (2006-7)

感染

遺傳

尿道阻塞

高血壓糖尿病

腎小球腎炎

DM 393

GN 217

Hong Kong Renal Registry香港醫院管理局腎病註冊

World

20002030

154 m370 m

55 m84 m

Developed Developing

99 m286 m

167338

329

182

524307

28391

809

228

423

186

09 16

20002030

In million subjects

102

81

71

211

255

127

78

THE GLOBAL BURDEN OF DIABETES (2000-2030)

WHO March 2003

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Consensus Workshop

Part 1 Detection of chronic kidney disease

Part 2 Evaluation and estimating progression of chronic kidney disease

Part 3 Measures to prevent the progression of chronic kidney disease

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)s2-7

Summary of the Consensus Statements (1)Summary of the Consensus Statements (1)

bull It is recommended to establish a global surveillance center (ISN Kidney Disease Data Centre or ISN KDDC) to coordinate worldwide standardized screening studies with standardized screening techniques in appropriate target groups to allow for the collection of clearly comparable data

bull It is recommended that patients diagnosed with diabetes and hypertension

should have regular screening for development of kidney disease

bull It is recommended that close relatives of patients with nephropathy due to diabetes hypertension and glomerulonephritis should also be the primary targets for screening to detect clinically silent kidney disease

bull No consensus was made on an exact age ldquocut-offrdquo for initiating CKD screening

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

SHAREScreening for Hong Kong Asymptomatic Renal

Population and Evaluation programme

普查計劃

腎康體健

Li PKT et al Kidney Int 2005 Apr(94)s36-40

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

TIME December 8 2003Newsweek Sept 4 2000

Percentage of incident patients

with diabetes 2006

data presented only for those countries from which relevant information was available All rates are unadjusted ^UK England Wales amp Northern Ireland (Scotland data reported separately) Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only Latest data for Canada Croatia amp Italy are for 2005 Data for France include 13 regions in 2005 amp 15 regions in 2006

1 Malaysia 5752 Mexico 4993 USA 4434 Japan 4255 Taiwan 424

8 Hong Kong 41

18 Australia 324

USRDS 2008

Diagnosis Distribution of NEW patients 2006 - 2007GN

217

Obstructive28

Unknown179

DM393

Others38

HTvascular106

Inherited cong30

Infection reflux08

新症病人之病因 (2006-7)

感染

遺傳

尿道阻塞

高血壓糖尿病

腎小球腎炎

DM 393

GN 217

Hong Kong Renal Registry香港醫院管理局腎病註冊

World

20002030

154 m370 m

55 m84 m

Developed Developing

99 m286 m

167338

329

182

524307

28391

809

228

423

186

09 16

20002030

In million subjects

102

81

71

211

255

127

78

THE GLOBAL BURDEN OF DIABETES (2000-2030)

WHO March 2003

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Consensus Workshop

Part 1 Detection of chronic kidney disease

Part 2 Evaluation and estimating progression of chronic kidney disease

Part 3 Measures to prevent the progression of chronic kidney disease

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)s2-7

Summary of the Consensus Statements (1)Summary of the Consensus Statements (1)

bull It is recommended to establish a global surveillance center (ISN Kidney Disease Data Centre or ISN KDDC) to coordinate worldwide standardized screening studies with standardized screening techniques in appropriate target groups to allow for the collection of clearly comparable data

bull It is recommended that patients diagnosed with diabetes and hypertension

should have regular screening for development of kidney disease

bull It is recommended that close relatives of patients with nephropathy due to diabetes hypertension and glomerulonephritis should also be the primary targets for screening to detect clinically silent kidney disease

bull No consensus was made on an exact age ldquocut-offrdquo for initiating CKD screening

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

SHAREScreening for Hong Kong Asymptomatic Renal

Population and Evaluation programme

普查計劃

腎康體健

Li PKT et al Kidney Int 2005 Apr(94)s36-40

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Percentage of incident patients

with diabetes 2006

data presented only for those countries from which relevant information was available All rates are unadjusted ^UK England Wales amp Northern Ireland (Scotland data reported separately) Data from Argentina Czech Republic Israel Japan Luxembourg Shanghai amp Taiwan are dialysis only Latest data for Canada Croatia amp Italy are for 2005 Data for France include 13 regions in 2005 amp 15 regions in 2006

1 Malaysia 5752 Mexico 4993 USA 4434 Japan 4255 Taiwan 424

8 Hong Kong 41

18 Australia 324

USRDS 2008

Diagnosis Distribution of NEW patients 2006 - 2007GN

217

Obstructive28

Unknown179

DM393

Others38

HTvascular106

Inherited cong30

Infection reflux08

新症病人之病因 (2006-7)

感染

遺傳

尿道阻塞

高血壓糖尿病

腎小球腎炎

DM 393

GN 217

Hong Kong Renal Registry香港醫院管理局腎病註冊

World

20002030

154 m370 m

55 m84 m

Developed Developing

99 m286 m

167338

329

182

524307

28391

809

228

423

186

09 16

20002030

In million subjects

102

81

71

211

255

127

78

THE GLOBAL BURDEN OF DIABETES (2000-2030)

WHO March 2003

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Consensus Workshop

Part 1 Detection of chronic kidney disease

Part 2 Evaluation and estimating progression of chronic kidney disease

Part 3 Measures to prevent the progression of chronic kidney disease

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)s2-7

Summary of the Consensus Statements (1)Summary of the Consensus Statements (1)

bull It is recommended to establish a global surveillance center (ISN Kidney Disease Data Centre or ISN KDDC) to coordinate worldwide standardized screening studies with standardized screening techniques in appropriate target groups to allow for the collection of clearly comparable data

bull It is recommended that patients diagnosed with diabetes and hypertension

should have regular screening for development of kidney disease

bull It is recommended that close relatives of patients with nephropathy due to diabetes hypertension and glomerulonephritis should also be the primary targets for screening to detect clinically silent kidney disease

bull No consensus was made on an exact age ldquocut-offrdquo for initiating CKD screening

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

SHAREScreening for Hong Kong Asymptomatic Renal

Population and Evaluation programme

普查計劃

腎康體健

Li PKT et al Kidney Int 2005 Apr(94)s36-40

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Diagnosis Distribution of NEW patients 2006 - 2007GN

217

Obstructive28

Unknown179

DM393

Others38

HTvascular106

Inherited cong30

Infection reflux08

新症病人之病因 (2006-7)

感染

遺傳

尿道阻塞

高血壓糖尿病

腎小球腎炎

DM 393

GN 217

Hong Kong Renal Registry香港醫院管理局腎病註冊

World

20002030

154 m370 m

55 m84 m

Developed Developing

99 m286 m

167338

329

182

524307

28391

809

228

423

186

09 16

20002030

In million subjects

102

81

71

211

255

127

78

THE GLOBAL BURDEN OF DIABETES (2000-2030)

WHO March 2003

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Consensus Workshop

Part 1 Detection of chronic kidney disease

Part 2 Evaluation and estimating progression of chronic kidney disease

Part 3 Measures to prevent the progression of chronic kidney disease

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)s2-7

Summary of the Consensus Statements (1)Summary of the Consensus Statements (1)

bull It is recommended to establish a global surveillance center (ISN Kidney Disease Data Centre or ISN KDDC) to coordinate worldwide standardized screening studies with standardized screening techniques in appropriate target groups to allow for the collection of clearly comparable data

bull It is recommended that patients diagnosed with diabetes and hypertension

should have regular screening for development of kidney disease

bull It is recommended that close relatives of patients with nephropathy due to diabetes hypertension and glomerulonephritis should also be the primary targets for screening to detect clinically silent kidney disease

bull No consensus was made on an exact age ldquocut-offrdquo for initiating CKD screening

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

SHAREScreening for Hong Kong Asymptomatic Renal

Population and Evaluation programme

普查計劃

腎康體健

Li PKT et al Kidney Int 2005 Apr(94)s36-40

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

World

20002030

154 m370 m

55 m84 m

Developed Developing

99 m286 m

167338

329

182

524307

28391

809

228

423

186

09 16

20002030

In million subjects

102

81

71

211

255

127

78

THE GLOBAL BURDEN OF DIABETES (2000-2030)

WHO March 2003

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Consensus Workshop

Part 1 Detection of chronic kidney disease

Part 2 Evaluation and estimating progression of chronic kidney disease

Part 3 Measures to prevent the progression of chronic kidney disease

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)s2-7

Summary of the Consensus Statements (1)Summary of the Consensus Statements (1)

bull It is recommended to establish a global surveillance center (ISN Kidney Disease Data Centre or ISN KDDC) to coordinate worldwide standardized screening studies with standardized screening techniques in appropriate target groups to allow for the collection of clearly comparable data

bull It is recommended that patients diagnosed with diabetes and hypertension

should have regular screening for development of kidney disease

bull It is recommended that close relatives of patients with nephropathy due to diabetes hypertension and glomerulonephritis should also be the primary targets for screening to detect clinically silent kidney disease

bull No consensus was made on an exact age ldquocut-offrdquo for initiating CKD screening

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

SHAREScreening for Hong Kong Asymptomatic Renal

Population and Evaluation programme

普查計劃

腎康體健

Li PKT et al Kidney Int 2005 Apr(94)s36-40

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Consensus Workshop

Part 1 Detection of chronic kidney disease

Part 2 Evaluation and estimating progression of chronic kidney disease

Part 3 Measures to prevent the progression of chronic kidney disease

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)s2-7

Summary of the Consensus Statements (1)Summary of the Consensus Statements (1)

bull It is recommended to establish a global surveillance center (ISN Kidney Disease Data Centre or ISN KDDC) to coordinate worldwide standardized screening studies with standardized screening techniques in appropriate target groups to allow for the collection of clearly comparable data

bull It is recommended that patients diagnosed with diabetes and hypertension

should have regular screening for development of kidney disease

bull It is recommended that close relatives of patients with nephropathy due to diabetes hypertension and glomerulonephritis should also be the primary targets for screening to detect clinically silent kidney disease

bull No consensus was made on an exact age ldquocut-offrdquo for initiating CKD screening

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

SHAREScreening for Hong Kong Asymptomatic Renal

Population and Evaluation programme

普查計劃

腎康體健

Li PKT et al Kidney Int 2005 Apr(94)s36-40

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Consensus Workshop

Part 1 Detection of chronic kidney disease

Part 2 Evaluation and estimating progression of chronic kidney disease

Part 3 Measures to prevent the progression of chronic kidney disease

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)s2-7

Summary of the Consensus Statements (1)Summary of the Consensus Statements (1)

bull It is recommended to establish a global surveillance center (ISN Kidney Disease Data Centre or ISN KDDC) to coordinate worldwide standardized screening studies with standardized screening techniques in appropriate target groups to allow for the collection of clearly comparable data

bull It is recommended that patients diagnosed with diabetes and hypertension

should have regular screening for development of kidney disease

bull It is recommended that close relatives of patients with nephropathy due to diabetes hypertension and glomerulonephritis should also be the primary targets for screening to detect clinically silent kidney disease

bull No consensus was made on an exact age ldquocut-offrdquo for initiating CKD screening

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

SHAREScreening for Hong Kong Asymptomatic Renal

Population and Evaluation programme

普查計劃

腎康體健

Li PKT et al Kidney Int 2005 Apr(94)s36-40

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Part 1 Detection of chronic kidney disease

Part 2 Evaluation and estimating progression of chronic kidney disease

Part 3 Measures to prevent the progression of chronic kidney disease

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)s2-7

Summary of the Consensus Statements (1)Summary of the Consensus Statements (1)

bull It is recommended to establish a global surveillance center (ISN Kidney Disease Data Centre or ISN KDDC) to coordinate worldwide standardized screening studies with standardized screening techniques in appropriate target groups to allow for the collection of clearly comparable data

bull It is recommended that patients diagnosed with diabetes and hypertension

should have regular screening for development of kidney disease

bull It is recommended that close relatives of patients with nephropathy due to diabetes hypertension and glomerulonephritis should also be the primary targets for screening to detect clinically silent kidney disease

bull No consensus was made on an exact age ldquocut-offrdquo for initiating CKD screening

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

SHAREScreening for Hong Kong Asymptomatic Renal

Population and Evaluation programme

普查計劃

腎康體健

Li PKT et al Kidney Int 2005 Apr(94)s36-40

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (1)Summary of the Consensus Statements (1)

bull It is recommended to establish a global surveillance center (ISN Kidney Disease Data Centre or ISN KDDC) to coordinate worldwide standardized screening studies with standardized screening techniques in appropriate target groups to allow for the collection of clearly comparable data

bull It is recommended that patients diagnosed with diabetes and hypertension

should have regular screening for development of kidney disease

bull It is recommended that close relatives of patients with nephropathy due to diabetes hypertension and glomerulonephritis should also be the primary targets for screening to detect clinically silent kidney disease

bull No consensus was made on an exact age ldquocut-offrdquo for initiating CKD screening

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

SHAREScreening for Hong Kong Asymptomatic Renal

Population and Evaluation programme

普查計劃

腎康體健

Li PKT et al Kidney Int 2005 Apr(94)s36-40

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

SHAREScreening for Hong Kong Asymptomatic Renal

Population and Evaluation programme

普查計劃

腎康體健

Li PKT et al Kidney Int 2005 Apr(94)s36-40

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Number of voluntary participants screened

Out of 1703 screened

1201 were apparently ldquohealthyrdquo

bullasymptomatic

bullno history of DM HT or CKDLi PKT et al Kidney Int 2005 Apr(94)s36-40

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Prevalence of abnormal urine results among asymptomatic subjects

Age Range 20-40 41-60 gt60 Total (95 CI)

N 226 641 334 1201Urine abnormalityUrine Protein (gt1+) 6 27 20 31 13 39 39 32 (22-42)Urine Sugar (gt1+) 3 13 11 17 7 21 21 17 (10-25)Urine RBC (gt1+) 13 58 91 142 62 186 166 138 (119-158)Urine Protein or RBC (gt1+) 18 8 104 162 70 21 192 160 (139-181)Any urine abnormality 20 88 113 176 76 228 209 174 (153-195)Urine Protein amp RBC (gt1+) 1 04 7 11 5 15 13 11 (05-17)

Li PKT et al Kidney Int 2005 Apr(94)S36-40

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Prevalence of Combined Abnormalitiesin the Asymptomatic Individuals

3322497Any BP or Urine abnormality

(1201)(334)(641)(226)No

Totalgt6041-6020-40Age

HT (BP gt14090 mmHg) or Microscopic hematuria orProteinuria orGlycosuria

Li PKT et al Kidney Int 2005 Apr(94)S36-40

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

50 (N=1703)

32 (N=1201)

241193 (N=14622)

54 (N=8585)

Prevalence of Proteinuria

Chinese (gt99)Caucasian (93) Asian (57) Aboriginal (08)

Chinese (77)Malay (11)Indian (9)

White (80)Black (11)Mexican (5)

Race

564 515 363 20-39 (46)Mean Age (yrs)

17031201

11247Not mentioned

189117169552 (min)

146228585

N (Total)N (Asymptomatic)

gt 20 yearsgt 25 yearsWorking adults

gt 20 yearsAge Range

20031999-20001997-20011988-1994Year of Screening

HKSARAustraliaSingaporeUSAData Source

SHAREAusDiabNKFSPrevention Program

NHANES IIIProgram Title

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Screening of silent kidney disease in Screening of silent kidney disease in relatives of chronic kidney disease relatives of chronic kidney disease

(CKD) patients in Hong Kong(CKD) patients in Hong Kong

bull This is an epidemiological study on the prevalence of silent renal diseaseurinary abnormalities or HT among the first degree relatives of existing renal patients

bull Inclusion Criteriandash First degree relatives of existing renal patients with

stage 1 to 5 CKD followed up in 10 hospitalsndash Age gt 18 years old

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Conclusions Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years

JAMA 20032903101-4

Boulware LE et al JAMA 20032903101-14

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hoerger TJ et al Ann Intern Med 2004 May 4140(9)689-99

Incremental CostIncremental Cost--Effectiveness Ratios Effectiveness Ratios for Diabetes Screeningfor Diabetes Screening

(Patients with HT)

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (3) Summary of the Consensus Statements (3) bull It is strongly recommended to have the relevant screening for the development of

CKD recognizing its close interrelationship with cardiovascular diabetic and chronic metabolic diseases Traditional cardiovascular disease risk factors should be screened in all patients with CKD These include documentation of smoking history measurement of blood pressure body weight body mass index fasting plasma glucose fasting lipid profile serum uric acid level and 12-lead electrocardiogram (ECG)

bull With the validation of GFR formulas in different ethnic groups it is endorsed that

GFR should be estimated from serum creatinine concentration at least yearlyin patients with CKD This should be done more often in patients with GFR below 60 mlmin173m2 GFR decline greater than 4 mlmin173m2 risk factors for faster progression or exposure to risk factors for acute GFR decline and in those undergoing treatment to slow progression

bull It is endorsed that CKD patients should be encouraged to reduce their body weight if over-weight adopt a healthy eating habit restrict their dietary salt intake cease smoking moderate their alcohol consumption and increase physical activity

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Zhang L et al J Am Soc Nephrol 2006172617-2621

CVD in participants stratified by different CVD in participants stratified by different estimated GFR (eGFR) stageestimated GFR (eGFR) stage

MI

Stroke

CVD

eGFRgt90 eGFR 60-89 eGFR 30-59

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients ndashndash Stage 3 to 4Stage 3 to 4

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

086 plusmn 085Proteinuria (gday)

398 plusmn 157Estimated GFR (mlmin173m2)

2144 plusmn 933Serum creatinine (micromoll)

203No of patients

modified MDRD equation validated in Chinese patients

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The average follow up was 524 plusmn 115 months

Forty-six patients (227) developed the primary composite end point

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Cardiovascular Diseases in Chinese Cardiovascular Diseases in Chinese PrePre--Dialysis CKD Patients Dialysis CKD Patients

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Szeto CCLi PKT J Am Soc Nephrol 2007 18 1966ndash1972

Primary cardiovascular end pointPrimary cardiovascular end point

p lt 00011385 ndash 18331593Charlsonrsquos comorbidity score

p = 00490957 ndash 09990978Baseline GFR

p = 00321029 ndash 19101402IMT quartile

P value95 CIAHRVariable

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

(African Americans)

(Polynesians)

30

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Causes of Glomerulonephritis (GN) leading to ESRF (2002)

Glomerulonephritis1 IgA Nephropathy 452 Lupus Nephritis 13 3 Focal Glomerulosclerosis 104 Mesangiocapillary nephritis 5 5 Membranous nephritis 4 6 Sclerosing Nephritis 87 Others 17

Hong Kong Renal Registry HA

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Course of IgA Nephropathy (IgAN)-Most common glomerulonephritis

Mean age of presentation 32 years

-68 of IgAN patients present with asymptomatic proteinuria andor microscopic hematuria ie No symptoms

-18 of patients progressed to ESRF in 10 years

-Risk factors of progression1 Hypertension2 Proteinuria gt 1 g day3 Impaired renal function4 High Histological grading

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Months

160140120100806040200

Cum

ulat

ive

Ren

al S

urvi

val

10

9

8

7

6

5

4

3

2

1

00

No at risk

168 152 126 31

Cum

ulat

ive

Ren

al S

urvi

val

920 at 1 year875 at 5 years 818 at 10 years

Li PKT et al Nephrol Dial Transplant 2002 1764-69

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Li PKT et al Nephrol Dial Transplant 2002 1764-69 Radford MG et al J Am Soc Nephrol 1997

2001 Hong Kong 168 818

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (4) Summary of the Consensus Statements (4)

bull It is endorsed to achieve the target for blood pressure control in CKD patients of below 13080 mmHg It is recommended that adjunctive dietary salt restrictionis invariably required Diuretics and multiple medications in addition to ACE inhibitorsangiotensin receptor blockers (ARB) may also be used to achieve the blood pressure targets

bull It is endorsed that glycemic control in diabetic patients with CKD should be

optimized to achieve a target fasting plasma glucose of lt72mmolL and a HbA1c level of lt7 Hypertensive diabetics and those with micro-albuminuria or macro-albuminuria whether hypertensive or not should be treated with either an ACEI or ARB

bull It is recognized that further large scale studies to substantiate the combined

use of ACEI and ARB are needed but that the cost of such combined therapy may be prohibitive for some countries

bull It is recommended that patients with CKD should be referred to a nephrologist

for evaluation when their creatinine clearance is lt 30mlminute173m2 or earlier in patients at risk of rapid progression or in whom doubt exists as to their diagnosis and prognosis

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

HONG KONG STUDY USING VALSARTAN IN IgA NEPHROPATHY

(HKVIN) ndashA DOUBLE-BLIND RANDOMIZED

PLACEBO-CONROLLED STUDY

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Prince of Wales Hospital Alice Ho Miu Ling Nethersole Hospital

Kwong Wah Hospital Princess Margaret Hospital

Tuen Mun Hospital United Christian Hospital

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

After 104 weeks

Valsartan group (N=54)18 plusmn 12 to 12 plusmn 12 gday

(p= 003)

Placebo group (N=55)23 plusmn 17 to 20 plusmn 17 gday

(p=072)

Valsartan treatment resulted in a 330 reduction in proteinuria

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Throughout the study periodFrom Week 0-Week 104

Significant reduction in the mean rate of GFR decline

- in the valsartan treated group - (-562 plusmn 679 mlminyear)

- compared with the placebo group - (-698 plusmn 617 mlminyear)

P = 0014

1 After adjustment for the blood pressure and baseline proteinuria

2 Treatment benefit was maintained until the end of study period

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Valsartan in IgA Nephropathy

Li PKT et al Am J Kidney Dis 2006 May47(5)751-60

(N=54)

(N=55)

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Paricalcitol

bull Suppress ndash macrophage infiltrationndash monocyte chemoattractant protein-1 (MCP-1)

productionndash transforming growth factor-beta-1 (TGF-β1) mRNA

and protein expressionndash phosphorylation of Smad2ndash these effects are amplified when blood pressure is

controlled via renin-angiotensin system blockade

Mizobuchi et al J Am Soc Nephrol 2007 18 1796-1806

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Use of Vit D in IgAN

bull Biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

bull Intervention Calcitriol 05 mcg twice weekly for 12 weeks

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Oral Oral calcitriolcalcitriol for the treatment of for the treatment of persistent persistent proteinuriaproteinuria in in IgAIgA nephropathynephropathy

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

prot

einu

ria (g

g-C

r)

05

10

15

20

25

30

35

40 p = 0004

0 week 12 week

Prot

einu

ria(g

g-C

r)

Week 0 Week 12

P=0004

148

198

One patient had transient hypercalcemia that normalized after dosage reduction (025mcg Twice per week)

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

percentage change in proteinuria

-40 -30 -20 -10 0 10

perc

enta

ge c

hang

e in

ser

um T

GF-β

-30

-20

-10

0

10

20

r = 0643 p = 002

Szeto CC hellip Li PKT Am J Kidney Dis 2008 May51(5)724-31

Perc

enta

ge c

hang

e in

TG

F-szlig

Percentage change in proteinuria

Oral Oral calcitriolcalcitriol in in IgAIgA nephropathynephropathy

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

vitamin Dclassical

PTH-suppression

RAS-suppression

immuno-modulating

effects

direct metabolic

effects

effects on myocardium

effects on vascular smooth muscle

BP lowering

survival benefit

CKD progression

VitVit D analogues in CKDD analogues in CKD

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

less TI damagenanaparicalcitolobstructive nephropathy

Tan et al [26]

less glomerulardamage

nareducecalcitriolThy11 glomerulonephritis

Migliori et al [25]

possibly a higher TI volume

less glomerulosclerosis

improvereduceparicalcitolsubtotallynephrectomy

Mizobuchi et al [24]

less glomerulosclerosis

nareduce22-oxacalcitriol

subtotallynephrectomy

Hirata et al [23]

no change in BP benefit not related to PTH

less glomerulosclerosis

nareducecalcitriolsubtotallynephrectomy

Schwarz et al [22]

Remarkshistologyrenal function

proteinuria

TreatmentModelStudy

Benefit

Animal studiesAnimal studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

no difference between treatment and placebo groups

reduced by 46 (95CI 17-65)

1 month

paricalcitol

24 CKD stage 2-3

prospective

Alborzi et al [29]

no difference before and after treatment

reduced (198 plusmn074 to 148 plusmn081 gg-Cr)

12 weeks

calcitriol10 IgAnephropathy

prospective

Szeto et al [28]

nareduced (OR 32 95CI 15-69)

24 weeks

paricalcitol

220 CKD stage 3-4

prospective

Agarwal et al [27]

no difference in the incidence of dialysis

na19 years

calcitriol1418 CKD stage 3-4

cohortShoben et al [21]

incidence rate ratio of dialysis 067 (95CI 046 to 097)

na21 years

calcitriol520 CKD stage 2-5

cohortKovesdy et al [20]

Renal functionProteinuriaFollow up

Treatment

PatientsTypeStudy

Szeto CC Li PKT Nephrology Dialysis Transplant Plus (in press)

Human studiesHuman studies examining the renal protective examining the renal protective effect of vitamin D analogueseffect of vitamin D analogues

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Causes of Causes of podocytopeniapodocytopenia

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Molecular anatomy of the Molecular anatomy of the podocytepodocyte foot process foot process actinactin cytoskeletoncytoskeleton

Mundel P Shankland SJ J Am Soc Nephrol 2002 Dec13(12)3005-15

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Wang G hellip Li PKT Nephron Clin Pract 2007106(4)c169-79

Messenger RNA Expression of Messenger RNA Expression of PodocytePodocyte-- Associated Molecules in the Associated Molecules in the Urinary SedimentUrinary Sediment of Patients with of Patients with Diabetic NephropathyDiabetic Nephropathy

Nephrin Podocin Synaptopodin

DN CTL DN CTL DN CTL

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Figure 3

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600

Hypertensive nephropathy

Kidney donors

podo

cyte

num

ber p

er g

lom

erul

us

0

200

400

600

800

1000

1200

1400

1600P lt 002

Podocyte number was significantly lower in patients with hypertensive nephrosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

proteinuria (gramday)

0 2 4 6 8 10 12 14 16 18

50e-5

10e-4

15e-4

20e-4

25e-4

30e-4

35e-4r = 0221P = 0277

GFR (mlmin)

0 20 40 60 80 100 120 140 160

00000

0001

0002

0003

0004

0005

0006r = 0536P lt 0005

(A) (B)

Figure 4

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Glomerular podocyte density significantly correlated with GFR

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Figure 5A

glomerulosclerosis ()0 20 40 60 80 100 120

00000

0001

0002

0003

0004

0005

0006r = -0400P lt 002

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Podocyte density inversely correlated with glomerulosclerosis

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Figure 5B

tubulointerstitial fibrosis ()0 20 40 60 80 100

00000

0001

0002

0003

0004

0005

0006r = -0578P lt 0001

podo

cyte

dens

ity(n

umbe

rμm

3 x

106 )

Wang G hellip Li PKT Am J Hypertens 2009 Mar22(3)300-6

Podocyte density inversely correlated with tubulointerstitial fibrosis

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Statins decrease proteinuria by protectingagainst podocyte apoptosis and subsequent podocyte depopulation

Cormack-Aboud FC et al Nephrol Dial Transplant 2009 24 404-12

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Hypertension incidence awareness treatment and control

22321253Germany24597041France

3122614China24524224US30506319UK19517958Italy

16405922CanadaControlledTreatedAwarePrevalence of diagnosed hypertension

Hypertension status ()

Chockalingam and Fodor Am J Hypertens 1998 Chamontin et al Am J Hypertens 1998 Marques-Vidal et al Q J Med 1997 Trenkwalder et al J Hypertens 1994 Vincenzi et al G Ital Cardiol 1992 Colhoun et al J Hypertens 1998 Franklin et al Hypertension 2001 Tao et al Chin Med J 1995

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Attained rate of target blood pressure in Attained rate of target blood pressure in nonnon--diabetic and diabetic hypertensivesdiabetic and diabetic hypertensives

Mori H et al Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan Hypertens Res 2006 29 143ndash151

12437 treated hypertensive patients from 1186 clinics and hospitals in 7 groups of prefectures in Japan collected in 2002

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

More can be done on control amp More can be done on control amp prevention of renal failureprevention of renal failure

Keller et al C Keller et al C DtschDtsch Med Med WochenschrWochenschr 20001252402000125240--44

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

1 Koro CE et al Diabetes Care 2004 2717ndash202 Liebl A Diabetologia 2002 45S23ndashS28

Perc

enta

ge o

f sub

ject

s0

20

40

60

80

100

le 65 gt 65

HbA1c ()

Perc

enta

ge o

f sub

ject

s

0

20

40

60

80

100

lt 7 ge 7

HbA1c ()

US1 EU2

Majority of type 2 diabetes patients in US and EU have inadequate glycemic control

31

69

36

64

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

CKD patients receiving ACE-IsARBs

NHANES III 1988ndash1994 amp NHANES 1999ndash2002 patients age 60 amp older patients with eGFRs of less than 15 mlmin173 m2 are excluded Sample size less than 30 or coefficient of variation is not less than 30 percent

USRDS 2005

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Barriers to Applying Good Evidences

PatientCompliance Cost Provider

Compliance Social factors

Evidence Based Knowledge amp Guidelines

Prevention of Chronic Kidney Disease

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Enhancing Primary Care in managing renal patientsEnhancing Primary Care in managing renal patientsQuality Outcomes Framework for CKD Quality Outcomes Framework for CKD (introduced Feb 2006 in UK) (introduced Feb 2006 in UK)

Klebe B et al Family Practice 2007 24(4)330-335

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

National Health InsuranceNational Health Insurancein Taiwanin Taiwan

Bureau of National Health Insurance2007

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Quality Assurance Program Quality Assurance Program in NHI Taiwanin NHI Taiwan

bull Designated budget for prevention

bull Incentives points for

ndash Achieving a target rate of eGFR decline in ndash Stages 3-5 CKD

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

PatientsrsquoKidney Health

Patient

General Internist

PrimaryCare Physicians

NephrologistTrainingEducationPublic AwarenessCoordination

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

UnreferredUnreferred Vs Known Populations to Renal ServicesVs Known Populations to Renal Services

Age Population Unreferred (pmp) Known (pmp) Known()

All 100 4708 pmp 846 pmp 152

John R et al Am J Kidney Dis 2004 May43(5)825-35

S Cr ge180 micromolL in men and ge135 micromolL in womenidentify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom

Between October 2000 and September 2001 a total of 13658 patients

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

UnreferredUnreferred chronic kidney disease chronic kidney disease a longitudinal study a longitudinal study

bull The percentage of known patients declined with age from approximately 50 in the younger agegroup to only 36 in patients 80 years and older

bull Referral of all patients with CKD is unrealistic and inappropriate

bull Management strategies need to be developed and implemented through collaboration between primary care and secondary care

John R et al Am J Kidney Dis 2004 May43(5)825-35

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Disease Management Disease Management ProgrammeProgramme

bull CKD stage 4 or 5bull by a community-based team of nurses

dietician and social worker1 Patient education 2 Medicine management3 Dietetic advice 4 Optimization of clinical management to

achieve clinical targetsRichards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Disease Management Disease Management ProgrammeProgrammebull A named nurse

bull Ready telephone and face-to-face access without the need for appointments in combination with proactive intervention from the clinical team

bull at a frequency dictated by the patientrsquos risk assessmentandor the patients themselves

bull Patient education and empowerment to become actively engaged in their own care and to raise awareness of and so reduce cardiovascular risk factors through lifestyle modification and appropriate medicine management

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Richards N et al Primary care-based disease management of CKD based on eGFRreporting improves patient outcomes Nephrol Dial Transplant 2008 Feb23(2)549-55

a fall in eGFR of ge 5 mlmin173 m2(n=122)

a fall of eGFR of ge 5 mlmin173 m2 (triangles n = 14)

[11]

a fall of eGFR of lt5 mlmin173 m2

(squares n = 73)[60]

a rise in eGFR of ge 5 mlmin173 m2

(circles n = 35)[29]

Primary Care based disease management Primary Care based disease management programmeprogramme for CKDfor CKD

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

New Opportunities for Early Renal Intervention New Opportunities for Early Renal Intervention by by ComputerisedComputerised Assessment Assessment (NEOERICA) (NEOERICA) studystudy

Klebe B et al Family Practice 2007 24(4)330-335

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Aims of the renal services Aims of the renal services information strategyinformation strategy

bull To educate the general public on CKD and to increase awareness especially in high-risk groups

bull To identify patients in primary care at risk of developing CKD

bull To make information available to patients diagnosed with CKD empowering them to make decisions about their treatment and ongoing management

bull Ensuring that IT systems are set up to support the diagnosis of acute kidney injury

bull Ensuring that IT systems in primary care support the appropriate referral of patients to nephrology

bull To support patients and their relatives in making informed choices about treatment options including conservative management

bull To provide decision support to secondary care clinicians from other disciplines providing management advice if required

Klebe B et al Family Practice 2007 24(4)330-335

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Kidney Help Trust in IndiaKidney Help Trust in Indiabull [Primary Health Centers (PHCs) in India

2 doctors and 2 paramedical workersEach PHC - population ~ 25000 Area of ~ 50 km2]

bull The medical officer supervises the work of the field workers (girls 15-18) and treats all the patients with the cheapest drugs reserpine and hydrochlorothiazide metformin and glibenclamide

bull Controlled hypertension to le 14090 in 96 of the hypertensives

bull Hba1c is down to le 7 in 52 of the diabetics

Mani MK Kidney Int 2006 70 821ndash823

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Disease Management (DM) in CKDDisease Management (DM) in CKD((in primary care levelin primary care level) )

For CKD patients not yet on dialysis the major goals of a Disease Management program are

1 Early identification of CKD patients and therapy to slow the progression of CKD

2 identification and management of the complications of CKD per se

3 identification and management of the complications of comorbid conditions

4 smooth transition to renal replacement therapy Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Potential barriers of a CKDendPotential barriers of a CKDend--stage renal stage renal disease disease DiseaseDisease Management programManagement program

bull Lack of awareness of the disease state among patients and health care providers

bull Late identification and referrals to a nephrologistbull Complex fragmented care delivered by multiple

providers in many different sites of care bull Reimbursement that does not align incentives for

all involved

Rastogi A et al Adv Chronic Kidney Dis 2008 Jan15(1)19-28

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

The Range of Intervention

TargetSocietyBehavioramp Values

TargetHighRiskBehavior

PredictivePreventiveMedicineGene RxStem Cell Rx

Biological markerIndividualScreening amp Rx

HealthPromotionPrograms

CommunityInfrastructure

National PoliciesTax IncentivesSocial Norms

UPSTREAMUPSTREAMHealthy Public PolicyHealthy Public Policy

DOWNSTREAMDOWNSTREAMPrevention and Curative FocusPrevention and Curative Focus

From ISN Bellagio Conference 2004

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Summary of the Consensus Statements (2) Summary of the Consensus Statements (2)

bull It is recommended to develop standardized region- (or nation-) specific guidelines It is envisaged that the ldquotailor-maderdquo tools for a particular region should provide reproducible and comparable results

bull It is asserted that kidney disease is already a significant public health concern

There should be national policies for both public health and medical professionals to educate their societies on the importance of screening and early detection of kidney disease on prevention

bull It is recommended to validate the current GFR estimation formulas based on

ethnicities in different parts of the world bull It is recommended to use albumin-creatinine ratios (ACR) to quantify

proteinuria and allow for follow-up However it is probably cost prohibitive to use ACR as a tool for primary renal disease screening (except in diabetic patients)

Li PKT Weening JJ Dirks J et al Kidney Int 2005 Apr(94)S2-7

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

World Kidney Day 2009 Steering Committee William Couser Paul Beerkens coshy Chairmen

Tom Reiser Jan Lantink Project Directors Georgi Abraham

Alan Collins John Feehally Joel Kopple

Philip Li Miguel Riella

Bernardo RodriguezshyIturbe Anne Wilson

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

World Kidney Day 2006

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Launching ceremony World Kidney Day Hong KongSunday 11 March 2007 Chater Garden

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

第三屆世界腎臟日在香港「腎友闔家同歡嘉年華」

三月十六日假九龍醫院舉行

World Kidney Day 2008

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

World Kidney Day 2009

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Roundtable Discussion on Dialysis Economics in Asia

Policies and Healthcare Financing

亞洲地區腹膜透析與醫療融資研討會

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Additional Patients Can Be Treated From Savings of More Use of Peritoneal Dialysis in China

(849)

0

1737

3526

5370

7270

9231

(2000)

0

2000

4000

6000

8000

10000

95 90 80 70 60 50 40Percent HD in Population

Patie

nts

Trea

ted

With

Sav

ings

CHINAIn year 5 with target 70 HD

Source amp Courtesy Chinese Medical Insurance Agency 2006 data presented in ISPD 2006 Dialysis Economics Roundtable

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Philip Kam-Tao Li Sing Leung Lui Chi Bon Leung Alex Wai-Yin Yu Evan Lee Paul M Just GeorgiAbraham Lynn AlmazanndashGomez Chiu Ching Huang Lai Seong Hooi Yoshindo Kawaguchi

Un I Kuok Kriang Tungsanga Tao Wang Andrew Kui-Man Wong Xue-Qing Yu and Wai Kei Loon behalf of the participants of the Roundtable Discussion on Dialysis Economics in Asia

Proceedings of the ISPD 2006 mdash The 11th Congress of the ISPDAugust 25 ndash 29 2006 Hong Kong Peritoneal Dialysis International Vol 27 (2007) Supplement 2

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

bull The rapidly growing number of ESRD patients is posing a heavy financial burden on the health care systems in all Asian countries

bull Wider utilization of PD which is more cost effectivethan HD can potentially alleviate this burden

bull The success of this strategy however requires fundamental changes in the health care reimbursement system so as to increase the incentiveof the clinicians or hospitals to initiate PD for their patients

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

bull More training of health care professionals on PD

bull enhanced correct information of PD as treatment option for renal failure patients

bull realigning incentives to support wider utilization of PD would enable the healthcare providers to offer quality treatment to more patients for a given budget

INCREASED UTILIZATION OF PERITONEAL DIALYSIS TO COPE WITH MOUNTING DEMANDFOR RENAL REPLACEMENT THERAPYmdashPERSPECTIVES FROM ASIAN COUNTRIES

Li PKT Lui SL Leung CB et al Perit Dial Int 2007 27 S59-61

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

Healthcare professionalsHealthcare professionals

bull Prevention

bull Dialysis

bull Transplantation

bull Research

bull Health Promotion

bull Recruitment

bull Training

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public

bull Data of Renal failure in Asia and the World

bull Challenges facing the CKD epidemic

bull Screening

bull CVD in CKD

bull Secondary Prevention- Trials in CKD

ndash Putting theory into practicendash Role of Primary Carendash Disease management Model

bull Promotion to public