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HFrEF and CKD: what do the guidelines say?

Prof. Adriaan Voors, CardiologistUniversity Medical Center Groningen

The Netherlands

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Disclosures• AAV received consultancy fees and/or research grants

from: Alere, AstraZeneca, Bayer, Cardio3Biosciences, Celladon, Merck/MSD, Novartis, Servier, Torrent, Trevena, Vifor.

• AAV was a member of the ESC 2012 Guidelines Committee

• AAV is supported by a grant from the European Commission: FP7-242209-BIOSTAT-CHF

• AAV is Clinical Established Investigator and supported by other grants of the Dutch Heart Foundation

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ESC 2012 HF Guidelines: General Statements

• The GFR is reduced in most patients with HF, especially if advanced, and renal function is a powerful independent predictor of prognosis in HF.

• Consider Causes:• Renal artery stenosis• Sodium and water depletion and hypotension• Volume overload, right heart failure, and renal venous congestion• Prostatic obstruction• Other drugs (e.g. NSAID, trimethoprim, gentamicin)• Use of RAAS-blockers• Use of thiazide and/or loop diuretics

McMurray et al. ESC-HF Guidelines; EJHF 2012

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• Contraindicated in known bilateral renal artery stenosis• Caution when significant renal dysfunction (creatinine

>221 μmol/L [>2.5 mg/dL] or eGFR <30 mL/min/1.73 m2)• In case of Worsening Renal Function:

• Creatinine ↑ ≤ 50% or 266 μmol/L (3 mg/dL)/eGFR <25 mL/min/1.73 m2, is acceptable

• Consider stopping nephrotoxic drugs or triamterene/amiloride and, if no signs of congestion, reducing the dose of diuretic

• Greater rises in creatinine: ½ dose RAAS-blockers• If creatinine ↑ by >100% or to >310 μmol/L (3.5 mg/dL)/eGFR

<20 mL/min/1.73 m2, stop RAAS-blocker

RAAS-blockers and CKD (appendix C and E)

McMurray et al. ESC-HF Guidelines; EJHF 2012

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• Significant renal dysfunction (creatinine >221 μmol/L [>2.5 mg/dL] or eGFR <30 mL/min/1.73 m2)–may be made worse by diuretic or patient may not respond to diuretic (especially thiazide diuretic)

• Worsening Renal function; • Hypovolaemia/dehydration? • Nephrotoxic agents, e.g. NSAIDs, trimethoprim? • Withhold MRA and/or thiazide? • Reduce dose of ACE inhibitor/ARB? • Haemofiltration/dialysis?

Loop diuretics and CKD (appendix F)

McMurray et al. ESC-HF Guidelines; EJHF 2012

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• Insufficient diuretic response/diuretic resistance: • Check compliance and fluid intake• Increase dose of diuretic• Consider switching from furosemide to bumetanide or

torasemide• Add MRA/increase dose of MRA • Combine loop diuretic and thiazide/metolazone• Consider short-term i.v. infusion of loop diuretic; • Consider ultrafiltration

Loop diuretics and CKD (appendix F)

McMurray et al. ESC-HF Guidelines; EJHF 2012

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WRF WHF Mortality re-Hosp0

5

10

15

20

25

30

Q1: GoodQ2Q3Q4Q5: Poor

Diuretic Response in AHFPROTECT: 2033 AHF patients;

Diuretic Response = kg weight loss/40 mg furosemide

*

*

**

*p<0.001

Valente et al. EHJ 2014

%

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ESC HF Guidelines 2012

McMurray et al. ESC-HF Guidelines; EJHF 2012

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CARESS-HF: primary endpoint

Bart et al. NEJM 2012

96 hours after randomization

N=188 ADHF pts with WRF

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ROSE-AHF: low dose dopamine in AHF

72 hour Urine volume

01,0002,0003,0004,0005,0006,0007,0008,0009,000

10,000

placebo

Urin

ary

Out

put (

L)

P=0.59

dopamine

Change in Cystatin C

0

0.02

0.04

0.06

0.08

0.1

0.12

0.14

placebo

dopamine

P=0.72

Mg/

dL

N=360 AHF patients with eGFR 15-60 ml/min

Chen et al. JAMA 2013

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• CKD and WRF often occur in HF• Always consider cause of WRF• RAAS-inhibitors: mild increase in creatinine allowed;

excessive increase: stop RAAS-blocker• Loop diuretic; less response in CKD• WRF: reduce stop loop diuretic, NSAIDs, trimethoprim,

MRA, thiazide, ACEi/ARB• Diuretic resistance: poor outcome• Ultrafiltration: as yet not proven to be effective• No benefit of low dose dopamine

Conclusions