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ACE Inhibitors in CKD
Dr Stuart Robertson
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Plan
• Why does CKD matter?• Indications for ACEi• Assessment & management of proteinuria• Mode of action• How to start and monitor• Risks of AKI
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CKD
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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
Ag
e-s
tan
da
rdis
ed
De
ath
Ra
te f
rom
A
ny
Ca
us
e (
pe
r 1
00
pa
tie
nts
/
ye
ar)
N Engl J Med 2004;351:1296-305.NEJM 2004; 351:1296
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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
Ag
e-s
tan
da
rdis
ed
Ra
te o
f C
ard
iov
as
cu
lar
Ev
en
ts (
pe
r 1
00
p
ati
en
ts /
ye
ar)
N Engl J Med 2004;351:1296-305.NEJM 2004; 351:1296
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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
eGFR
Ag
e-s
tan
da
rdis
ed
Ra
te o
f H
os
pit
ilis
ati
on
(p
er
10
0 p
ati
en
ts /
ye
ar)
N Engl J Med 2004;351:1296-305.NEJM 2004; 351:1296
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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.
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CKD is Treatable
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ACE Inhibitors & ARBs
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Indications
Heart Failure
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Indications
Hypertension
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Indications
Proteinuria
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NICE - Proteinuria
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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
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Proteinuria & Mortality
NHANES II - J Am Soc Nephrol 2002;13:745-753
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Proteinuria - Renal Decline
MDRD Study - NEJM 1994 330(13):877
Proteinuria g/day
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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
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ACEi vs Others
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ACEi vs Others
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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
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NICE
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ACEi – Mode of Action
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Renal Autoregulation
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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
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Advice Leaflet
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Risk of AKI
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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
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Enjoy Lunch!