1. EVALUATION AND MANAGEMENT OF CHRONIC KIDNEY DISEASE Dr. D.Adu Ghana College CPD August 2011

2. 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

3. 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

4. CHRONIC RENAL FAILURE IN AFRICA

5. 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

6. Serum creatinine an inaccurate measure of GFR

7. 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)

8. 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

9. ACR vrs 24 hr Urine Albumin

10. K/DOQI Stages of CKD StageDescriptionGFR mL/min/1.73m 2 1Kidney damage with normal or ↑GFR >90 2Kidney damage with mild ↓GFR 60-89 3Moderate ↓GFR30-59 4Severe ↓GFR15-29 5Kidney failure<15 or dialysis

11. CKD PREVALENCE WORLDWIDE CountryStudyCKD 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

12. Does CKD Matter? Few patients with CKD 1-3 progress to renal failure But patients with CKD have a high mortality from cardiovascular disease

13. 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

14. 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.

15. Does CKD Matter? CKD associated with increased risk of cardiovascular disease Proteinuria and albuminuria associated with increased risk of cardiovascular disease

16. 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

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

18. UK Renal Registry 11 th Annual Report 2008

19. 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?

20. 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

21. 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/1.73m 2 Blood pressure control overall was poor

22. 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

23. 1 In diabetic and non-diabetic renal disease the following slow the progression of renal impairment Treatment of hypertension Reducing proteinuria Angiotensin blockade

24. 2 In diabetic and non-diabetic renal disease the following may reduce cardiovascular morbidity Stopping smoking Statins Aspirin

25. REMNANT KIDNEY MODEL Brenner B.M.

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

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

28. Early Treatment Makes a Difference Brenner, et al., 2001

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

30. Meta Analysis: Lower Mean BP Results in Slower Rates of Decline in GFR in Diabetics and Non-Diabetics9598101104107110113116119 r = 0.69; P < 0.05 MAP (mmHg) GFR (mL/min/year) 130/85140/90 Untreated HTN 0 -2 -4 -6 -8 -10 -12 -14 Parving 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

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

32. REIN Study: ACE Inhibition in Proteinuric Non- Diabetic Nephropathy Baseline SBP∆ SBPBaseline DBP∆ DBP Ramipril149.8-5.8 mmHg92.4-4.2 mmHg Placebo148.0-3.4 mmHg91.3-3.4 mmHg 0 0 6 6 12 18 24 30 36 100 80 60 40 20 0 100 80 60 40 20 0 Ramipril Placebo P=0.02 The GISEN Group. Lancet. 1997;349:1857–1863. % of patients without combined endpoint* *Combined endpoint = doubling of baseline serum creatinine concentration or end stage renal failure www.hypertensiononline.org

33. 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

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

35. ACE Inhibitors Slow Progression of CKD in Type 1 Diabetes Lewis et al, NEJM 1993;329:1456-62 p=0.007 n=202 vs 207 Years follow-up 0 30 20 10 00.51.02.0 2.51.53.03.5 % with doubling creatinine 40 50 Captopril Placebo 4.0

36. 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* Cumulative % of patients with event Months 240123648 554 583 Placebo Losartan Risk reduction=16% P=0.02 762 751 689 692 295 329 36 52 Placebo † (n) Losartan † (n)

37. Angiotensin Blockade Provides Greater Renoprotection Than Other Blood Pressure drugs in Patients with Diabetic and Non-Diabetic Nephropathy

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

39. 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.

40. ANGIOTENSIN BLOCKADE CONCLUSIONS Benefits of angiotensin blockade only seen in patients with significant proteinuria (>0.5 G/day)

41. 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

42. 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

43. 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

44. 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

45. Should we Stop ACEI or ARB in Advanced CKD

46. 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

47. Should we Stop ACEI or ARB in Advanced CKD YES

48. What is the Size of the Problem

49. Estimated CKD in Ghana using International Prevalence StageDescriptionGFRPrevalence (%) Number in Ghana 1Kidney damage with normal GFR >903.3792,000 2Mild decrease in GFR 60-903.072,000 3Moderate decrease in GFR 30-604.3103,2000 4Severe decrease in GFR 15-300.248,000 5Kidney failure<150.124,000

50. 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

51. EDUCATION OF THE PUBLIC

52. 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

53. 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

54. 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