EVALUATION AND MANAGEMENT OF CHRONIC KIDNEY DISEASE

Dr. D.Adu

Ghana College CPD August 2011

LEARNING OBJECTIVES

• To describe the methods for assessing chronic kidney disease

• To understand the KDOQI classification for staging of CKD

• To understand the epidemiologic burden of CKD• To evaluate the efficacy of medical interventions

needed to slow progression of chronic kidney disease

WHAT IS CHRONIC KIDNEY DISEASE

• The persistent and usually progressive reduction of kidney function as measured by the glomerular filtration rate

• Retention of urea and creatinine

• Proteinuria and/or haematuria

• Hypertension

• Late stage anaemia and bone disease

CHRONIC RENAL FAILURE IN AFRICA

0 20 40 60 80 100

MATEKOLE

AKINSOLA

ABBOUD

SEEDAT (B)

SEEDAT (I)

USRDS

HYPERT GN PYELON DIABETES OTHER

Key Investigations

• Urine Dipstick test for blood and protein• Urine microscopy for rbc, wbc and casts• Urine albumin/creatinine ratio or protein/creatinine

ratio• Creatinine and eGFR• Ultrasound kidneys

Serum creatinine an inaccurate measure of GFR

GFR

• Serum creatinine only rises when kidney function is half normal!

• MDRD (Modification of diet in renal disease study) GFR validated (normal 90-120ml/min)

GFR

• http://www.renal.org/eGFRcalc/GFR.pl

Calculate GFR using the MDRD formula:  GFR = 186 X (Creatinine x 0.0113)-1.154 X age-0.203  Women = Multiply x 0.742 Black = Multiply x 1.21

Calculation available online

UA

LB/C

R

UALB. G/24HR0 1 2 3 4 5 6 7 8 9 10

0

100

200

300

400

500

600

700

800

900

1000

ACR vrs 24 hr Urine Albumin

K/DOQI Stages of CKD Stage Description GFR mL/min/1.73m2

1 Kidney damage with normal or ↑GFR

>90

2 Kidney damage with mild ↓GFR

60-89

3 Moderate ↓GFR 30-59

4 Severe ↓GFR 15-29

5 Kidney failure <15 or dialysis

CKD PREVALENCE WORLDWIDE

Country Study CKD Prevalence

95% CI

USA Coresh et al. 2007

13.1% 12.0%-14.1%

Australia White et al. 2010

13.4% 11.1-16.1

Norway Hallan et al. 2006

10.2% (se 0.5)

UK Stevens et al. 2007

8.5% (ckd 3-5)

Nigeria Afolabi et al. 2009

10.4% (ckd 3-5)

DRC Sumaili et al. 2008

12.4% 11-15.1

Does CKD Matter?

• Few patients with CKD 1-3 progress to renal failure

• But patients with CKD have a high mortality from cardiovascular disease

Crude incidence rate of end-stage renal disease by category of estimated glomerular filtration rate and category of albuminuria

van der Velde M et al. Kidney Int. 79(12):1341-52

Age-Standardized Rates of Death from Any Cause (Panel A), Cardiovascular Events (Panel B), and Hospitalization (Panel C), According to the Estimated GFR among 1,120,295 Ambulatory Adults.

Go AS et al. N Engl J Med 2004;351:1296-1305.

Does CKD Matter?

• CKD associated with increased risk of cardiovascular disease

• Proteinuria and albuminuria associated with increased risk of cardiovascular disease

DRIVERS FOR CKD IN GHANA

• ≈ 30% of the Ghanaian population older than 40 years have hypertension

• 6.3% of adult Ghanaians have diabetes mellitus

• Glomerulonephritis• Genetic factors: APOL-1 and MYH9

polymorphisms• Herbal nephrotoxins

9.5

16.2

0

2

4

6

810

12

14

16

18

%

2006

2009

KIDNEY DISEASE AS A PROPORTION OFMEDICAL ADMISSIONS AT KORLE BU

HOSPITAL

10% OF DEATHS ON MEDICAL WARDS DUE TO CKD

UK Renal Registry 11th Annual Report 2008

Figure 3.5: Incident rates by age and gender in 2007

0

100

200

300

400

500

600

700

20-2

4

25-2

9

30-3

4

35-3

9

40-4

4

45-4

9

50-5

4

55-5

9

60-6

4

65-6

9

70-7

4

75-7

9

80-8

4

85+

Age bandR

ate

per

mill

ion

popu

latio

n

MalesAll UKFemales

CKD ADMISIONS BY AGE KORLE BU

0

20

40

60

80

100

120

11-20

21-30

31-40

41-50

51-60

61-70

71-80

81-90

91-100

AGE

Nu

mb

er o

f su

bje

cts

MALE

FEMALE

TOTAL

CKD GHANA HOSPITAL QUESTIONS

• Why is the proportion of CKD amongst medical admissions in Ghana increasing

• Why are the peak ages for CKD 20-50 in Ghana as compared with 65-85 in the UK?

CKD IN HYPERTENSIVE PATIENTS IN GHANA

53.1

8.7

10.4

23.7

3.11

0

10

20

30

40

50

60

70

80

90

100

% o

f s

ub

jec

ts

CKD 5

CKD 4

CKD 3

CKD 2

CKD 1

NO CKD

Osafo C, Mate-Kole M, Affram K, Adu D. Prevalence of chronic kidney disease in hypertensive patients in Ghana. Renal Failure. 2011;33(4):388-92.

27.8% OF HYPERTENSIVE ADULTS IN GHANA HAVE CKD STAGES 3-5

CKD IN HYPERTENSIVE PATIENTS IN GHANA

• Overall 46.9% of patients had CKD

• 27.8% of patients with hypertension had CKD 3-5 i.e. a GFR of less than 60ml/min/1.73m2

• Blood pressure control overall was poor

CONCLUSIONS 1

• We report a high prevalence of CKD in hypertensive patients in Ghana

• The cause of the CKD is not known from our study but may be due to hypertension

• The implications of our study if confirmed are of great public health significance

1

In diabetic and non-diabetic renal disease the following slow the progression of renal impairment

• Treatment of hypertension

• Reducing proteinuria

• Angiotensin blockade

2

In diabetic and non-diabetic renal disease the following may reduce cardiovascular morbidity

• Stopping smoking

• Statins

• Aspirin

REMNANT KIDNEY MODEL

right nephrectomy

2/3 ligation ofleft A. renalis

Brenner B.M.

Hyperfiltration hypothesis (Brenner)

Reduced nephron mass

Glomerular hyperfiltration

Glomerulosclerosis

Glomerular hypertension

Progressive renal failure PROTEINURIA

Pathologic Processes Leading to Progressive Glomerular Injury and Proteinuria

Increasedglomerularpressure

Ang II

Urinary protein

Efferent arteriolar

constriction

=angiotensin AT1 receptor

ACE INH OR ARB

Increased filtration

Afferent arteriolardilatation

Ang II

Early Treatment Makes a Difference

Brenner, et al., 2001

What is the evidence that blood pressure control retards progression of renal disease

Meta Analysis: Lower Mean BP Results in Slower Rates of Decline in GFR in Diabetics and Non-Diabetics

9595 9898 101101 104104 107107 110110 113113 116116 119119

r = 0.69; P < 0.05

MAP (mmHg)

GF

R (

mL

/min

/yea

r)

130/85 140/90

UntreatedHTN

00

-2-2

-4-4

-6-6

-8-8

-10-10

-12-12

-14-14Parving HH, et al. Br Med J. 1989. Moschio G, et al. N Engl J Med. 1996.Viberti GC, et al. JAMA. 1993. Bakris GL, et al. Kidney Int. 1996.Klahr S, et al. N Eng J. Med 1994. Bakris GL. Hypertension. 1997.Hebert L, et al. Kidney Int. 1994. The GISEN Group. Lancet. 1997.Lebovitz H, et al. Kidney Int. 1994.

Bakris GL, et al. Am J Kidney Dis. 2000;36(3):646-661., www.hypertensiononline.org

What is the evidence that blood pressure control and angiotensin blockade retards progression of

non diabetic renal disease

REIN Study: ACE Inhibition in Proteinuric Non-Diabetic Nephropathy

Baseline SBP ∆ SBP Baseline DBP ∆ DBP

Ramipril 149.8 -5.8 mmHg 92.4 -4.2 mmHg

Placebo 148.0 -3.4 mmHg 91.3 -3.4 mmHg

00 66 1212 1818 2424 3030 3636

100

80

60

40

20

0

100

80

60

40

20

0

RamiprilRamipril

PlaceboPlacebo

P=0.02P=0.02

The GISEN Group. Lancet. 1997;349:1857–1863.

% o

f pati

ents

wit

hout

com

bin

ed e

ndp

oin

t*

*Combined endpoint = doubling of baseline serum creatinine concentration or end stage renal failure

www.hypertensiononline.org

Copyright restrictions may apply.

Agodoa, L. Y. et al. JAMA 2001;285:2719-2728.

Cumulative Incidence of Renal Events and Death with ACE Inhibition in African-Americans

What is the evidence that blood pressure control and angiotensin blockade retards progression of

diabetic renal disease

ACE Inhibitors Slow Progression of CKD in Type 1 Diabetes

Lewis et al, NEJM 1993;329:1456-62

p=0.007n=202 vs 207

Years follow-up

0

30

20

10

0 0.5 1.0 2.0 2.51.5 3.0 3.5

% w

ith d

oubl

ing

crea

tinin

e

40

50

Captopril

Placebo

4.0

0

10

20

30

40

50

Brenner BM, et al. N Engl J Med. 2001;345(12):861-869.©2001 Massachusetts Medical Society. All rights reserved.

†In combination with open-label diuretic, calcium channel blocker, beta-blocker, alpha-blocker, and/or centrally acting agent *doubling of serum creatinine, end stage renal disease, death

RENAAL Patients Reaching the Primary Composite Endpoint*

Cu

mu

lati

ve %

of

pati

en

ts w

ith

even

t

Months240 12 36 48

554

583

Placebo

Losartan

Risk reduction=16%

P=0.02

762

751

689

692

295

329

36

52

Placebo† (n)

Losartan† (n)

Angiotensin Blockade Provides Greater Renoprotection

Than Other Blood Pressure drugs in Patients with Diabetic and Non-Diabetic Nephropathy

Who benefits from Angiotensin Treatment and Good Blood Pressure Control? Does Proteinuria Matter?

Copyright ©2007 American Society of Nephrology

Kent, D. M. et al. J Am Soc Nephrol 2007;18:1959-1965

Risk-stratified outcome rates (doubling of baseline serum creatinine or kidney failure) in patients (with non-diabetic kidney disease) treated with ACE-inhibitors) with and without urinary protein excretion >=500 mg/d.

ANGIOTENSIN BLOCKADE CONCLUSIONS

• Benefits of angiotensin blockade only seen in patients with significant proteinuria (>0.5 G/day)

Cumulative Incidence of the Composite Primary Outcome, According to Baseline Proteinuria Status (AASK Study)

Appel LJ et al. N Engl J Med 2010;363:918-929.

x

No proteinuria good prognosis and no

protection from good BP control

BLOOD PRESSURE CONTROL AND CKD

• Good blood pressure control slows progression of CKD in patients with proteinuria and has no effect in patients without proteinuria

Target Blood Pressure

• 125/75 if 24 hour urine protein >1G or ACR >100

• 130/80 if 24 hour urine protein<1G or ACR<100

• If aged > 65 aim for 140/80

What to do with ACEi or ARB induced reduction in GFR

• Check chemistry 2 weeks after starting these drugs and 4 weeks after each change in dose

• If GFR drop >20% discontinue drug and refer ? Renal artery stenosis /ischaemia

Should we Stop ACEI or ARB in Advanced CKD

Changes in eGFR after stopping ACEi/ARB in patients with advanced CKD.

Ahmed A K et al. Nephrol. Dial. Transplant. 2010;25:3977-3982

© The Author 2009. Published by Oxford University Press [on behalf of ERA-EDTA]. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Should we Stop ACEI or ARB in Advanced CKD

YES

What is the Size of the Problem

Estimated CKD in Ghana using International Prevalence

Stage Description GFR Prevalence (%)

Number in Ghana

1 Kidney damage with normal GFR

>90 3.3 792,000

2 Mild decrease in GFR

60-90 3.0 72,000

3 Moderate decrease in GFR

30-60 4.3 103,2000

4 Severe decrease in GFR

15-30 0.2 48,000

5 Kidney failure <15 0.1 24,000

Known CKD <1% of population

Unrecognised CKD

10% of population

• Public education of CKD• Strategies required for prevention of progression• Screen for BP, glucose and proteinuria at Health Centres• Treat with ACEI

EDUCATION OF THE PUBLIC

Conclusion 1

• CKD is common in medical admissions in Ghana

• CKD occurs at a younger age (20-50) in Ghana than in the UK

• CKD more common in men than in women

• CKD common in hypertensive patients in Ghana

Conclusion 2

In diabetic and non-diabetic renal disease

• Treatment of hypertension slows the progression of renal impairment

• Reducing proteinuria slows the progression of renal impairment

• Angiotensin blockade slows the progression of renal impairment

Statement:

• Any intervention that reduces the incidence or

progression of diabetic/hypertensive renal disease will

have a HUGE IMPACT

• on life expectancy

• quality of life

• costs to society and healthcare payers