CVD in CKD：：：：Asian Experience

CVD in CKD：：：：Asian Experience

KDIGO-CVD Conference2010.10.29. London, UKKDIGO-CVD Conference2010.10.29. London, UK

Asian ExperienceAsian Experience

Kunitoshi IsekiDialysis Unit, University Hospital of The Ryukyus,

Okinawa, Japan

Kunitoshi IsekiDialysis Unit, University Hospital of The Ryukyus,

Okinawa, Japan

1. General Japanese population

Prevalence of “lifestyle related disease”

Trends of BMI & proteinuria among screened subjects

Studies on CKD vs. CVD

eGFR, proteinuria, and underlying kidney disease

2. ESRD population: demographics

The Japanese Society for Dialysis Therapy (JSDT) registry

Underlying kidney disease, age, gender

Contents of the PresentationContents of the Presentation

Underlying kidney disease, age, gender

Causes of death: GP vs. ESRD

3. Factors related to increased mortality risk among ESRD patients

Pre-HD blood pressure & pulse rate

RAS vs. non-RAS drugs

Treatment of hypertension: ongoing RCT

4. Asian Forum of CKD Initiative (ACKDI)

Pan Asian CKD registry

Rapid increase in ESRD patients in China

Lifestyle related diseaseLifestyle related disease

3,500

740

880

600

1,100

Hypertension

DM

Pre-DM

Dyslipidemia

Obesity 1,100

500

30～～～～50

1,330

X10,000

Obesity

Hyperuricemia

Gout

CKD

Japanese eGFR formula

Matsuo S et al. Am J Kidney Dis 53:982-992, 2009

20-29 30-39 40-49 50-59 60-69 70≤≤≤≤ years0

10

20

30

40

%

men1984

1994

2004

16.9

19.918.0

22.8

28.9

25.3 26.4

32.7

22.224.6

30.8

19.7

23.8

29.7

25.5

15.214.0

9.4

Prevalence of obesity, Prevalence of obesity, BMIBMI≥≥2525

MHWL 2004

20-29 30-39 40-49 50-59 60-69 70≤≤≤≤ years0

10

20

30

40

%

women1984

1994

2004

7.7 7.35.4

13.2 13.0

8.3

20.422.4

17.9

28.425.7

24.1

29.7 29.930.1

26.724.6 24.5

20-29 30-39 40-49 50-59 60-69 70≤≤≤≤ years

4.0

5.0

6.0

7.0

8.0

1980

1990

2000

4.0

5.0

6.0

7.0

8.0

Pre

vale

nce,

%

Prevalence of ProteinuriaPrevalence of Proteinuria

men women

0.0

1.0

2.0

3.0

4.0

30-39 40-49 50-59 60-69 70- Total30-39 40-49 50-59 60-69 70- Total

0.0

1.0

2.0

3.0

4.0

Pre

vale

nce,

%

Age Age

CKD Prevalence: Hisayama StudyCKD Prevalence: Hisayama Study

Men

Women

CKD stage3-5

*P<0.01 vs. 1974

Age≥40, age-adjusted*

*

*

Pre

vale

nce,

%

10

12

14

16

18

Nagata M et al. NDT 252: 2557-2564, 2010

1974 1988 2002

Pre

vale

nce,

%

0

2

4

6

8

Men Women

Log-Rank p<0.01

Cu

mm

ula

tive r

ate

, % Log-Rank

p<0.01

CKD (+)

35.6% in 12yrs

CKD (+)

22.0% in 12yrs

*p<0.05 vs. CKD (-)

CKD (-)

RR

1.0

1.5

2.0

2.5

1.01.0

1.4

1.0

1.9

1.0

1.2

*

*CKD (+)

50

40

30

20

CKD vs CVD :Hisayama studyCKD vs CVD :Hisayama study

Ninomiya T et al. Kidney Int 68: 228-236, 2005

0 2 4 6 8 10 12

Cu

mm

ula

tive r

ate

, %

yrs

12.0% in 12yrs

7.8% in 12yrs

†age, sex, hypertension, ECG, DM, BMI, TC, TG, HDL-C, homocysteine, hs-CRP, smoking, alcohol

0

0.5

1.0

CVD IHD CI

0.7

CH

CKD (+) = GFR < 60 ml/min/1.73m2

10

0

0 2 4 6 8 10 12

N=2,634, 1988-2000, not-adjusted N=2,634, 1988-2000, adjusted

10

15

20

AMI

ESRD

CKD vs CVD :OkinawaCKD vs CVD :OkinawaC

um

ula

tive I

ncid

en

ce o

f C

ard

iovascu

lar

Dis

ease o

r E

SR

D,

pe

r 1

,00

0 p

ati

en

t d

uri

ng

th

e s

tud

y p

eri

od

Stroke

0

Iseki K et al. Vasc Dis Prev 3;327-333, 2006

<60 ≥60Age

Chronic kidney disease

6,108 398 3,382 4,095

<60 ≥60

Number of screenees

＋＋＋＋－－－－ ＋＋＋＋－－－－

Cu

mu

lati

ve I

ncid

en

ce o

f C

ard

iovascu

lar

Dis

ease o

r E

SR

D,

pe

r 1

,00

0 p

ati

en

t d

uri

ng

th

e s

tud

y p

eri

od

5

CVD deaths are related with proteinuria and low eGFR

Men Women

CKD vs CVD :Ibaraki studyCKD vs CVD :Ibaraki study

3

4

3

4

2.15 *

4.00*

Irie F et al. Kidney Int 69: 1264-1271, 2006

UP-UP+

GFR≥60

GFR<600

1

2

0

1

2

UP-UP+

GFR≥60

GFR<60

1.53

2.15

1.00 1.39

*

*

1.58

1.002.02

*

*

＊＊＊＊:P<0.05

NH

O

Life style in “Edo” periodLife style in “Edo” period

O

HNｚｚｚｚ

NHNH

NH

O

1790 K Santo

Odds Ratio (95% CI) CVD Death

Primary CKD 1.00 10 4

Hypertension 2.87 (1.37-6.02) 20 5

Diabetes Mellitus 11.88 (4.58-30.83) 26 7

Different Clinical outcomes for CVDDifferent Clinical outcomes for CVDThe Gonryo studyThe Gonryo study

Nakayama M et al. Clin Exp Nephrol 14: 333-339, 2010

N=2,692 CKD patients, 1-yr cohort studyAdjusted for age, gender, Hb, proteinuria, SBP, BMI, hyperlipidemia, DM, steroid, smoking, history of CVD

Diabetes Mellitus 11.88 (4.58-30.83) 26 7

Other CKD 3.59 (1.81-7.09) 13 8

ESRD 113, CVD 69, death 24, lost F/U 200

TP12TP18

TP20

TP27

C3 C4

C5C5

C8

TP9TP25

Death

CKD

(Early detection

& treatment

CKD

(Symptomatic) Intervention

Natural Course to Dialysis : Markov modelNatural Course to Dialysis : Markov model

TP20

TP21(C6)TP13

TP8(C2)

TP3(C1)

C1

TP23(C7)

C2

C6

C7

TP19

Death

ESRDESRD

Ischemic

Events

+/-The Japanese Society of Nephrology (JSN) Task Force for the Validation of Urine Examination as an Universal Screening (VALUE-US)

Prevalence of Hypertension Prevalence of Hypertension

60%

80%

100%

Nationwide Specific Health Check and Guidance System in Japan, N=332,174

15-2930-44

45-5960-89

90-

-

+/+-

2+0%

20%

40%

eGFR

UP

15.0%

20.0%

25.0%

30.0%

Prevalence of CVD HistoryPrevalence of CVD History

0.0%

5.0%

10.0%

15.0%

-

+/+-

2+

UP15-2930-44

45-5960-89

90-eGFR

Nationwide Specific Health Check and Guidance System in Japan, N=332,174

Incidence by renal disease :ESRDIncidence by renal disease :ESRDN

um

ber

of

pati

en

ts

12,000

16,000

CGN

DM

18,000

Mean age 1997 2007 2008

CGN 60.5 66.4 66.9

DM 62.5 65.4 65.6

NScl 71.4 73.7 74.0

10,000

14,000

JSDT

Year

Nu

mb

er

of

pati

en

ts

0

2,000

4,000

6,000

8,000

'83 '84 '85 '86 '87 '88 '89 '90 '91 '92 '93 '94 '95 '96 '97 '98 '99 '00 '01 '02 '03 '04 '05 '06

NScl

Unknown

'07 '08 '09 '10

Mean Age of Patients :ESRDMean Age of Patients :ESRDA

ge,

years

Incident

Prevalent

55

60

65

70

Year

JSDT

Ag

e,

years

40

45

50

55

'83 '84 '85 '86 '87 '88 '89 '90 '91 '92 '93 '94 '95 '96 '97 '98 '99 '00 '01 '02 '03 '04 '05 '06 '07 '08 '09 '10

per

millio

n p

op

ula

tio

n

Incidence by gender :ESRDIncidence by gender :ESRD

Men

Women250

300

350

400

450In

cid

en

ce,

per

millio

n p

op

ula

tio

n

JSDT

Women

Difference

0

50

100

150

200

'83 '84 '85 '86 '87 '88 '89 '90 '91 '92 '93 '94 '95 '96 '97 '98 '99 '00 '01 '02 '03 '04 '05 '06 '07 '08 '09 '10

Year

Causes of Death in Prevalent PatientsCauses of Death in Prevalent PatientsP

erc

en

tag

e,

%

Cardiac

Infection

20

25

30

35

40

JSDT

Year

Perc

en

tag

e,

%

Stroke

Malignancies

Acute myocardial infarction

0

5

10

15

20

'83 '84 '85 '86 '87 '88 '89 '90 '91 '92 '93 '94 '95 '96 '97 '98 '99 '00 '01 '02 '03 '04 '05 '06 '07 '08 '09 '10

Causes of Death in General PopulationCauses of Death in General PopulationN

of

death

Cardiac

Malignancies

200,000

250,000

300,000

350,000

Year

N o

f d

eath

Stroke

0

50,000

100,000

150,000

1980 1985 1990 1995 2000 2005

Pneumonia

Kidney Failure

Decrepitude

MHWL

Annual Mortality rateAnnual Mortality rate

%

10

14

16

18

20

women

men

ESRDPatients

General Population

12

Mo

rtali

ty r

ate

0

2

4

6

8

10

40 50 60 70 80

Population

Age, years

Mo

rtali

ty r

ate

JSDT, MHWL

Prognosis: Prognosis: ESRD pts vs.CVD ptsESRD pts vs.CVD pts

Su

rviv

al

0.6

0.8

1.0

Observation, months

Iseki K et al. Clin Exp Nephrol 5:109-113, 2001

Su

rviv

al

0

0.2

0.4

0 12 24 36 48 60 72 84 96 108 120

GP: acute MI

GP: stroke

ESRD

Survival of Dialysis PatientsSurvival of Dialysis Patients

JSDT database

1. Pre-HD blood pressure (N=163,668)

2. Pre-HD pulse rate (N=147,702)

Prevalent patients cohort

* Mean Age 63.6 yrs, DM 31.4%, BMI 21.1* Mean Age 63.6 yrs, DM 31.4%, BMI 21.1

* Mean Vintage 8.0yrs (more than 10,000 pts; >25 yrs)

* History of CVD

AMI 6.1%

CH 3.7%

CI 11.8%

Amputation 2.4%

Ad

juste

d o

dd

s r

ati

o (

95%

CI)

2

3

4

5

none

yes

Anti-hypertensive drugs

PrePre--HD systolic BP vs. SurvivalHD systolic BP vs. SurvivalA

dju

ste

d o

dd

s r

ati

o (

95%

CI)

<100 100- 120- 140- 160- 180- 200-

Pre-HD systolic BP, mmHg

0

4,56114,18232,47635,86416,9123,309372

9863,71011,30417,73114,4646,2421,555none

yes

1

2

reference

Iseki K et al. Nephron Clinical practice 113; C183-C190, 2009

2

3

Anti-hypertensive drugs

Ad

juste

d o

dd

s r

ati

o (

95%

CI)

PrePre--HD diastolic BP vs. SurvivalHD diastolic BP vs. Survival

none

yes

Pre-HD diastolic BP, mmHg

<60 60- 70- 80- 90- 100- 110-

2,3446,68317,00431,78129,18615,9774,701

7472,4966,99614,81715,82010,5154,601none

yes

0

1

reference

Ad

juste

d o

dd

s r

ati

o (

95%

CI)

Iseki K et al. Nephron Clinical practice 113; C183-C190, 2009

Effects of drug treatmentEffects of drug treatment

0.6

0.8

1.0

reference

Ad

juste

d o

dd

s r

ati

o (

95%

CI)

Iseki K et al. Nephron Clinical Practice 113; C183-C190, 2009

0.0

0.2

0.4

RAS(-) RAS(+)Anti-hypertensivedrugs(-)

Anti-hypertensive drugs

Ad

juste

d o

dd

s r

ati

o (

95%

CI)

Nu

mb

er

of

Pati

en

ts

Distribution of Pulse RateDistribution of Pulse Rate

3,000

4,000

5,000

6,000

Pre-HD Pulse Rate, bmp

Nu

mb

er

of

Pati

en

ts

2,000

3,000

0

1,000

40- 50- 60- 70- 80- 90- 100- 110- 120-

Iseki K et al. NDT2010, in press

2.0

2.5

3.0

3.5

4.0

Adjusted

Not Adjusted

Od

ds r

ati

o (

95%

CI)

Pulse Rate and SurvivalPulse Rate and Survival

Pre HD pulse rate, per min

0.5

1.0

1.5

2.0

40- 50- 60- 70- 80- 90- 100- 110-

reference

0

Od

ds r

ati

o (

95%

CI)

Iseki K et al. NDT2010, in press

OCTOPUS

Olmesartan Clinical Trial in OkinawanPatients Under OKIDS

Cochran Renal Group

www.cochran-renal.org

CRG010600030

OCTOPUS

Iseki K et al. Clin Exp Nephrol 13; 145-151, 2009

ProtocolProtocol

DW control

Olmesartan

>1 monthDW control

Best treatment

Non RAS inhibitors

RAS inhibitors

Hypertension

screening

Follow-up（（（（3 yrs））））

Baseline data

・・・・Exclusion & inclusion criteria

・・・・Informed & written consent

・・・・Randomized by sex & DM

End of follow-up

・・・・Safety

EventsDeath, CVD

Prevalent HD Patients in Okinawa 2005N=3,529

Preliminary Screening at Contracted Units

N=1,240 RAS (-) : N=640

RAS (+) : N=600

Informed ConsentN=533

Randomization 2006 June to 2008 June

N=469

Follow-up by 2011 June

Excluded1. Not signed2. Against inclusion criteria

(N=49)(N=15)

Target BP<140/90mmHg at Pre-HD

Blood pressure: PreBlood pressure: Pre--HD vs. HomeHD vs. Home

#P<0.0001, *P<0.005

Co-chairs: Kunitoshi Iseki, Vivekanand Jha

WG 2, Pan Asian CKD WG 2, Pan Asian CKD RegistryRegistry

Co-chairs: Kunitoshi Iseki, Vivekanand Jha

Members : Evan Lee, Jafar H Tazeen,

Lynn A Gomez, Randal Faull,

Zaki Morad, T Criang, Chin Ho Jun,

Toshiaki Monkawa, Vlado Perkovic

To provide concrete data of CKD registry on

Aim of the Pan Asian Aim of the Pan Asian RegistryRegistry

To provide concrete data of CKD registry on

prevalence, incidence based on the sources,

collecting method (proteinuria, Albuminuria, eGFR)

• regional difference

• set-up outcome variables

• find unique problems in Asian countries

• What are the key outcomes of CKD?

Questions addressed Questions addressed with the registrywith the registry

• What are the key outcomes of CKD?

Risk of CVD and mortality with CKD;

may be different among Asians

Prevalence of IgA GN;

vary by ethnic background and geographical area

Rapid increase in ESRD in ChinaRapid increase in ESRD in China

• Total number on maintenance dialysis:

41,755 (1999)

65,074 (2007)

120,000 (2009, not complete yet)

• Prevalence of ESRD, per million population• Prevalence of ESRD, per million population

33.2 (1999)

51.7 (2008)

92.3 (2009, 1.3 billion)

Fan Fan Hou. ISN-NEXUS Kyoto 2010

Within 5 years, N of ESRD becomes larger than JSDT!

Similarities

•Increasing prevalence of CKD & ESRD

•CKD as a risk factor of CVD

Summary of the presentationSummary of the presentation

CKD and CVD:

Asians vs. non-Asian countries

•CKD as a risk factor of CVD

Dissimilarity

Effect of gender, obesity, and underlying kidney disease

•More ESRD than CVD

•Better survival of ESRD patients in Japan