1. ACE Inhibitors in CKD Dr Stuart Robertson

2. Plan Why does CKD matter? Indications for ACEi Assessment & management of proteinuria Mode of action How to start and monitor Risks of AKI

3. CKD

4. Risk Factor for Death N Engl J Med 2004;351:1296-305. NEJM 2004; 351:1296

5. Risk Factor for Cardiovascular Disease N Engl J Med 2004;351:1296-305. NEJM 2004; 351:1296

6. CKD as Risk Factor for Hospitalisation N Engl J Med 2004;351:1296-305. NEJM 2004; 351:1296

7. CKD is an Independent Risk Factor eGFRDeath fromCardiovascularHospitalisation Any CauseEvent >601.001.001.00 45-591.21.41.1 30-441.82.01.5 15-293.22.82.1 <155.93.43.1 The analyses were adjusted for age, sex, income, education, use or nonuse of dialysis, and the presence or absence of prior coronary heart disease, prior chronic heart failure, prior ischemic stroke or transient ischemic attack, prior peripheral arterial disease, diabetes mellitus, hypertension, dyslipidemia, cancer, a serum albumin level of 3.5 g per deciliter or less, dementia, cirrhosis or chronic liver disease, chronic lung disease, documented proteinuria, and prior hospitalizations. N Engl J Med 2004;351:1296-305.

8. CKD is Treatable

9. ACE Inhibitors & ARBs

10. Indications Heart Failure

11. Indications Hypertension

13. Indications Proteinuria

14. NICE - Proteinuria

15. Proteinuria Assessment Microalbuminuria screening in diabetes – ACR Quantification of proteinuria – PCR Logic –ACR more sensitive but 6x more expensive –PCR is a meaningful number PCR 150mg/mmol = 1500mg/day protein

16. Proteinuria & Mortality NHANES II - J Am Soc Nephrol 2002;13:745-753

17. Proteinuria - Renal Decline MDRD Study - NEJM 1994 330(13):877 Proteinuria g/day

18. Importance of Proteinuria MDRD Study - NEJM 1994 330(13):877 More proteinuria = more rapid decline in renal function Better BP control reduces decline at any amount of proteinuria

19. ACEi vs Others

21. ACE Benefit NON-DM patients with Proteinuria “Benazepril for Advanced Chronic Renal Failure” Non-diabetic patients with proteinuria Group1 Creat 130 – 265 Group2 Creat 265 - 440 NEJM 2006; 354 Endpoint=Creatx2, ESRF or death

22. NICE

23. ACEi – Mode of Action

25. Renal Autoregulation

26. Titration of ACEi If eGFR declines 20% overall, need to balance symptoms, mortality etc. and determine optimum dose Baseline eGFR Start ACEi eGFR at 7-10 days eGFR stable  eGFR >20%  eGFR <20% Titrate ACEi ↑ Stop ACEi Monitor weekly Deteriorating eGFR Stable eGFR

27. Advice Leaflet

29. Risk of AKI

30. What Did He Say? ACEi are indicated in hypertension, heart failure & proteinuric renal disease (DM & non-DM) ACEi are beneficial even in advanced CKD with appropriate monitoring Avoid addition of NSAIDs to ACEi & diuretic Pathophysiology of decline in renal function related to ACEi Commend the patient advice leaflet to reduce ACEi related AKI

31. Enjoy Lunch!