Diuretic Resistance in Heart Failure
Purpose of Review
Diuretic resistance (DR) occurs along a spectrum of relative severity and contributes to worsening of acute heart failure (AHF) during an inpatient stay. This review gives an overview of mechanisms of DR with a focus on loop diuretics and summarizes the current literature regarding the prognostic value of diuretic efficiency and predictors of natriuretic response in AHF.
The pharmacokinetics of diuretics are impaired in chronic heart failure, but little is known about mechanisms of DR in AHF. Almost all diuresis after administration of a loop diuretic dose occurs in the first few hours after administration and within-dose DR can develop. Recent studies suggest that DR at the level of the nephron may be more important than defects in diuretic delivery to the tubule. Because loop diuretics induce natriuresis, urine sodium (UNa) concentration may serve as a functional, physiological, and direct measure for diuretic responsiveness to a given loop diuretic dose.
Identifying and targeting individuals with DR for more aggressive, tailored therapy represents an important opportunity to improve outcomes. A better understanding of the mechanistic underpinnings of DR in AHF is needed to identify additional biomarkers and guide future trials and therapies.
KeywordsAcute heart failure Loop diuretics Diuretic resistance Spot urine sodium Biomarkers
Compliance with Ethical Standards
Conflict of Interest
Richa Gupta declares no conflicts of interest.
Jeffrey Testani received consultancy fees and/or research grants from AstraZeneca, Boehringer Ingelheim, Sanofi, Abbott, FIRE1, Sequana Medical, Otsuka, Bristol Myers Squibb, Reprieve Medical, Cardionomic, and 3ive labs.
Sean Collins received consultancy fees and/or research grants from Novartis, Vixiar, Ortho Clinical, NIH, AHRQ, PCORI, DOD, AHA, and CREAVO.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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