ACE Inhibitors in CKD Dr Stuart Robertson

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

CKD

Risk Factor for Death N Engl J Med 2004;351: NEJM 2004; 351:1296

Risk Factor for Cardiovascular Disease N Engl J Med 2004;351: NEJM 2004; 351:1296

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

CKD is an Independent Risk Factor eGFRDeath fromCardiovascularHospitalisation Any CauseEvent > < 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:

CKD is Treatable

ACE Inhibitors & ARBs

Indications Heart Failure

Indications Hypertension

Indications Proteinuria

NICE - Proteinuria

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

Proteinuria & Mortality NHANES II - J Am Soc Nephrol 2002;13:

Proteinuria - Renal Decline MDRD Study - NEJM (13):877 Proteinuria g/day

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

ACEi vs Others

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

NICE

ACEi – Mode of Action

Renal Autoregulation

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

Advice Leaflet

Risk of AKI

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

Enjoy Lunch!