ACE Hemmer / ARB absetzen bei CKD Stadium 4-5 · 2019. 5. 7. · • ACEh/ARB bis eGFR 15-20 ml/min nicht absetzen, sofern keine NW (CV Vorteile und renale Vorteile bei Proteinurie

ACE Hemmer / ARB absetzen bei CKD Stadium 4-5 ?

Johannes Mann

KfH Nierenzentrum München Isoldenstraßeund

Med. Klinik 4, Friedrich Alexander Universität Erlangen-Nürnberg

Heidelberg, April 2019

I report the following potential dualities of interest :

Consultant: Boehringer, Celgene, Fresenius, Novo Nordisk, Vifor

Employee: KfH Research Support: European Union, Canadian Institutes

of Health Research, Univ. of Uppsala, AbbVie, Celgene, Idorsia, Novo Nordisk, Sanofi

Speaker’s Bureau: Boehringer, Fresenius, Medice, Novartis, Novo Nordisk, Roche, Sandoz

Stock/Shareholder: NoneTravel Support: In conjunction with above-mentioned

activities

Frage an 703 Nephrologen (USA, KDOQI)

“Sollen ACE Hemmer / ARB abgesetzt

werden, wenn die eGFR bei progredienter

CKD unter 20 ml/min/1,73 m2 fällt? „

Frage an 703 Nephrologen (USA, KDOQI)

“Sollen ACE Hemmer / ARB abgesetzt

werden, wenn die eGFR bei progredienter

CKD unter 20 ml/min/1,73 m2 fällt? „

Nein: 53,8%Ja: 46,2%



1) Vorteile der ACE Hemmer bei CKD-Für die Nieren-Für kardiovaskuläres System

2) Nebenwirkungen der ACE Hemmer bei CKD3) Warum eventuell absetzen ?

(Jafar et al Ann Int Med 2001;135:73-87)

RR for ESRD: ACEI vs conventional drugs(meta-analysis of 1,860 patients of 11 trials)

Lancet 2005;366:2026-34

Rel. risk for ESKD

Lancet 2005;366:2026-34

Rel. risk for ESKD- Association with BP -

Main outcomes in patients with CKD Mann, Gerstein, Pogue, Bosch, Yusuf, Ann Int. Med 2001;134:629-36

Prim. outcome

MI

CV Death All Death

PlaceboRamipril

Even

ts (p

er 1

000

pt-y

rs)

MI, stroke, CV death

MI

CV death Death

no CKD CKD no CKD CKD

no CKD CKD no CKD CKD

No CKD N= 6000, CKD N= 3500)

Prim. Endpunkt:Kreatinin x2,Dialyse, Tod

Group 1:Krea 1.5-3 mg/dlGroup 2:Krea 3.01-5 mg/dl

Group 2: placebo

Group 1: benazepril

Group 2: benazepril

Blutdruck und Proteinurie

Beobachtungsstudie in Taiwan: 28.500 Pat. mit S-Kreatinin >6mg/dl,

50% mit, 50% ohne ACE Hemmer

Dialyse Dialyse oder Tod

Follow-up (months) Follow-up (months)

ACE/ARB

non-user

ACE/A

RB no

n-user

ACE/A

RB us

er

ACE/ARB

user




2) Nebenwirkungen der ACE Hemmer bei CKD3) Warum eventuell absetzen ?

ONTARGET: Risk of hyperkalemia in subgroups at high renal risk

Tobe, Clase, Gao, Teo, Yusuf, Mann. Circulation 2011;123:1098–1107

a

60eGFR Urine

albu

min

Macro-AMicro-A.Norm-A.

Macro-A

Micro-A.

Norm-A.

% with

K > 5.5 mmol/L

Hyperkalemia, RAS-i and CKD

Hyper-K develops in approx. 10% of patients treated with RAS-i, within the 1st year.

Hyper-K in hospitalized patients is attributed to RASi in 15-38% of cases.

Reardon et al., Arch Int Med 1998;158:26 and Palmer, NEJM 2004;351:585

Hyperkalemia, & K-binders patiromer and ZS-9 in RAS-i treated patients

Weir et al, NEJM 2015;372:211


Weir et al, NEJM 2015;372:211 Anker et al., Eur J Heart Fail 2015;17:1050


Weir et al, NEJM 2015;372:211 Anker et al., Eur J Heart Fail 2015;17:1050

Kalium

wird ges

enkt.

Werden

auch En

dpunkte

verbes

sert

durch di

e Mögli

chkeit R

AS-i we

iter zu g

eben?




2) Nebenwirkungen der ACE Hemmer bei CKD3) Warum eventuell ACE Hemmer absetzen ?

Langfristiger Verlauf der GFR: Abhängigkeit vom initialen Verlauf

Apperloo et al., Kidney Int 1997;51:793-7

Stopping inhibitors of the renin-angiotensin system in patients with advanced CKD, N= 44

Ahmed et al, NDT 2010;25:3977

Stopping inhibitors of the renin-angiotensin system in patients with advanced CKD

Ahmed et al, NDT 2010;25:3977

Before After stopping

BP (mmHg) 134/68 139/72

UPC (g/g) 0.8 1.25

Gonc

alve

sAR,

El N

ahas

M e

t al

Nep

hron

Clin

ical

Pra

ctic

e 20

11: 1

19: 3

48-3

54

A >5ml improvement in GFR was predictive of dialysis or death

Angiotensin Converting Enzyme inhibitor (ACEi) / Angiotensin Receptor Blocker (ARB) – To STOP OR Not

in Advanced Renal Disease

Prof Sunil BhandariConsultant NephrologistHonorary Clinical ProfessorInternational Director RCPE

EudraCT Number: 2013-003798-82MHRA CTA: 21411/0242/001-0001 (12th December 2013).Research Ethics Committee: Yorkshire and The Humber, Leeds East. Ref: 13/YH/0394. (29th January 2014).

No ExcludedNot Meeting CriteriaDeclinedOther Reason

3 Ye

ar

Follo

w-U

p 3-monthly visits - routine tests (eGFR, FBC, BCP, urinary PCR), BP, documentation of ESA dose, adverse events, compliance and changes in medication

Extra tests at annual visits

- QOL questionnaire, weight and BMI, 6-minute walk test, ECG, and bloods for C-reactive protein, cystatin-C, NT-proBNP, ACE/renin levels and biomarkers

Yes

CKD patients stage 4-5ACEi/ARB treatments

Eligible for STOP-ACEi study?

Randomise1:1 ratio, N=410

Experimental Arm:Discontinue ACEi/ARB

N=205

Control Arm:Continue ACEi/ARB

N=205

2 ye

ars r

ecru

itmen

t3

year

s fol

low

-up

TARGET BP

Participating sites – 38 UK Renal Units

Frage an 703 Nephrologen (USA)

• “Sollen ACE Hemmer / ARB abgesetzt werden,

wenn die eGFR bei progredienter CKD unter

20 ml/min/1,73 m2 fällt? „

• Nein: 53,8%• Ja: 46,2%

Meine Schlussfolgerung

• ACEh/ARB bis eGFR 15-20 ml/min nicht absetzen,

sofern keine NW (CV Vorteile und renale Vorteile

bei Proteinurie >1g/g).

• Wenn eGFR 15-20 ml/min erreicht und eGFR

Verlust >3ml/min/Jahr: ACEh/ARB pausieren und

eGFR, BD, Urin-Eiweiß beobachten, dann neu

entscheiden.

QJM: An International Journal of Medicine, Volume 101, Issue 7, 28 March 2008, Pages 519–527, https://doi.org/10.1093/qjmed/hcn039The content of this slide may be subject to copyright: please see the slide notes for details.

Nierenarterienstenose und ACE Hemmer

HF studies provide little information to direct care in advanced CKD - patients with significant renal dysfunction were excluded

Ahmed/Jorna/Bhandari DOI: Nephron 10.1159/000447068

DM as a compelling indication for use of RAAS blockers: systematic review & meta-analysis of randomized trials?

Bangalore S et al. BMJ 2016; 352:i438.

19 RCTs25414 participants

No difference in • Death• CV death• MI• Angina• Stroke• HF• Renal Outcomes

Effect of RAAS blockade in adults with diabetes mellitus and advanced CKD not on dialysis: a systematic review and meta-analysis

Nephrol Dial Transplant. Published online July 02, 2017. doi:10.1093/ndt/gfx072



FIGURE 2 All-cause mortality and CV mortality: ACEIs/ARBs versus placebo/other antihypertensive treatment.



FIGURE 3 Non-fatal CV events: ACEIs/ARBs versus placebo/other antihypertensive treatment.



Figure 4: Need for RRT/doubling of serum creatinine: ACEIs/ARBs versus placebo/other antihypertensive treatment



FIGURE 5 eGFR/CrCl (ml/min/1.73 m2), end-of-treatment values: ACEIs/ARBs versus placebo/other antihypertensive treatment.

Angiotensin Converting Enzyme Inhibitor, Angiotensin Receptor Blocker Use, and Mortality in Patients With Chronic Kidney Disease

Miklos Z. Molnar; Kamyar KalantarZadeh et al J Am Coll Cardiol. 2014;63(7):650658.

Figure 1: survival probability of treated and untreated patients in the propensity score matched cohort, with ACEI/ARB treatment -association with lower mortality in both intention to treat and as treated models.

Change in eGFR from Run-in

Documents

ACE Hemmer / ARB absetzen bei CKD Stadium 4-5 · 2019. 5. 7. · • ACEh/ARB bis eGFR 15-20 ml/min nicht absetzen, sofern keine NW (CV Vorteile und renale Vorteile bei Proteinurie