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

0.76 1.08

4.76

11.36

14.14

0

2

4

6

8

10

12

14

16

>60 45-59 30-44 15-29 <15

eGFR

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N Engl J Med 2004;351:1296-305.NEJM 2004; 351:1296

Risk Factor for Cardiovascular Disease

2.11 3.65

11.29

21.8

36.6

0

5

10

15

20

25

30

35

40

>60 45-59 30-44 15-29 <15

eGFR

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N Engl J Med 2004;351:1296-305.NEJM 2004; 351:1296

CKD as Risk Factor for Hospitalisation

13.54 17.22

45.26

86.75

144.61

0

20

40

60

80

100

120

140

160

>60 45-59 30-44 15-29 <15

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N Engl J Med 2004;351:1296-305.NEJM 2004; 351:1296

CKD is an Independent Risk Factor

eGFR Death from Cardiovascular HospitalisationAny Cause Event

>60 1.00 1.00 1.0045-59 1.2 1.4 1.130-44 1.8 2.0 1.515-29 3.2 2.8 2.1<15 5.9 3.4 3.1

The analyses were adjusted for age, sex, income, education, use or nonuseof dialysis, and the presence or absence of prior coronary heart disease, priorchronic heart failure, prior ischemic stroke or transient ischemic attack, priorperipheral arterial disease, diabetes mellitus, hypertension, dyslipidemia, cancer,a serum albumin level of 3.5 g per deciliter or less, dementia, cirrhosis orchronic liver disease, chronic lung disease, documented proteinuria, and priorhospitalizations.

N Engl J Med 2004;351:1296-305.

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;13:745-753

Proteinuria - Renal Decline

MDRD Study - NEJM 1994 330(13):877

Proteinuria g/day

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

ACEi vs Others

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 265 - 440

NEJM 2006; 354

Endpoint=Creatx2, ESRF or death

NICE

ACEi – Mode of Action

Renal Autoregulation

Titration of ACEi

If eGFR declines <20% with each ↑ACEi dose but >20% overall, need to balance symptoms, mortality etc. and determine optimum dose

Baseline eGFRStart ACEi

eGFR at 7-10 days

eGFR stable eGFR>20%eGFR

<20%

Titrate ACEi ↑ Stop ACEiMonitor weekly

Deteriorating eGFRStable 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!