EVALUATION AND MANAGEMENT OF CHRONIC KIDNEY DISEASE Dr

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

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 e. GFR • 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 -120 ml/min)

GFR • http: //www. renal. org/e. GFRcalc/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

ACR vrs 24 hr Urine Albumin 1000 900 800 UALB/CR 700 600 500 400 300 200 100 0 0 1 2 3 4 5 6 UALB. G/24 HR 7 8 9 10

K/DOQI Stages of CKD Stage Description GFR m. L/min/1. 73 m 2 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 95% CI Prevalence 13. 1% 12. 0%-14. 1% USA Coresh et al. 2007 Australia White et al. 2010 13. 4% 11. 1 -16. 1 Norway Hallan et al. 2006 Stevens et al. 2007 10. 2% (se 0. 5) Afolabi et al. 2009 Sumaili et al. 2008 10. 4% (ckd 35) 12. 4% UK Nigeria DRC 8. 5% (ckd 3 -5) 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 MYH 9 polymorphisms • Herbal nephrotoxins

KIDNEY DISEASE AS A PROPORTION OFMEDICAL ADMISSIONS AT KORLE BU HOSPITAL 10% OF DEATHS ON MEDICAL WARDS DUE TO CKD

UK Renal Registry 11 th Annual Report 2008

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?

27. 8% OF HYPERTENSIVE ADULTS IN GHANA HAVE CKD STAGES 3 -5 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.

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 60 ml/min/1. 73 m 2 • 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 Brenner B. M.

Hyperfiltration hypothesis (Brenner) Reduced nephron mass Glomerular hypertension Glomerular hyperfiltration Glomerulosclerosis Progressive renal failure PROTEINURIA

Pathologic Processes Leading to Progressive Glomerular Injury and Proteinuria Urinary protein Increased filtration Afferent arteriolar dilatation =angiotensin AT 1 receptor Increased glomerular pressure Efferent arteriolar constriction Ang II ACE INH OR ARB

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 MAP (mm. Hg) GFR (m. L/min/year) 95 0 98 101 104 107 110 -2 113 116 119 r = 0. 69; P < 0. 05 -4 -6 Untreated HTN -8 -10 -12 -14 130/85 140/90 Parving HH, et al. Br Med J. 1989. Viberti GC, et al. JAMA. 1993. Klahr S, et al. N Eng J. Med 1994. Hebert L, et al. Kidney Int. 1994. Lebovitz H, et al. Kidney Int. 1994. Moschio G, et al. N Engl J Med. 1996. Bakris GL, et al. Kidney Int. 1996. Bakris GL. Hypertension. 1997. The GISEN Group. Lancet. 1997. 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 % of patients without combined endpoint* 100 80 Ramipril 60 40 P=0. 02 20 Placebo 0 0 6 12 18 24 30 36 Baseline SBP ∆ SBP Baseline DBP ∆ DBP Ramipril 149. 8 -5. 8 mm. Hg 92. 4 -4. 2 mm. Hg Placebo 148. 0 -3. 4 mm. Hg 91. 3 -3. 4 mm. Hg *Combined endpoint = doubling of baseline serum creatinine concentration or end stage renal failure The GISEN Group. Lancet. 1997; 349: 1857– 1863. www. hypertensiononline. org

Cumulative Incidence of Renal Events and Death with ACE Inhibition in African-Americans Agodoa, L. Y. et al. JAMA 2001; 285: 2719 -2728. Copyright restrictions may apply.

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

% with doubling creatinine ACE Inhibitors Slow Progression of CKD in Type 1 Diabetes 50 40 p=0. 007 n=202 vs 207 Placebo 30 20 10 Captopril 0 0 0. 5 1. 0 1. 5 2. 0 2. 5 Years follow-up 3. 0 3. 5 4. 0 Lewis et al, NEJM 1993; 329: 145662

Cumulative % of patients with event RENAAL Patients Reaching the Primary Composite Endpoint* Placebo Risk reduction=16% P=0. 02 Losartan 0 12 24 Months 36 48 Placebo† (n) 762 689 554 295 36 Losartan† (n) 751 692 583 329 52 †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 Brenner BM, et al. N Engl J Med. 2001; 345(12): 861 -869. © 2001 Massachusetts Medical Society. All rights reserved.

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?

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. Kent, D. M. et al. J Am Soc Nephrol 2007; 18: 1959 -1965 Copyright © 2007 American Society of Nephrology

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) No proteinuria good prognosis and no protection from good BP control x Appel LJ et al. N Engl J Med 2010; 363: 918 -929.

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 >1 G or ACR >100 • 130/80 if 24 hour urine protein<1 G 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 e. GFR 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 60 -90 in GFR 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

• Public education of CKD • Strategies required for prevention of progression • Screen for BP, glucose and proteinuria at Health Centres • Treat with ACEI Known CKD <1% of population Unrecognised CKD 10% of population

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