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  • Review Article
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Diuretic response in acute heart failure—pathophysiology, evaluation, and therapy

Nature Reviews Cardiology volume 12, pages 184–192 (2015)Cite this article

Subjects

Key Points

  • The administration of loop diuretics to achieve decongestion is the cornerstone of therapy for acute heart failure

  • Impaired diuretic response is a common complication in patients with acute heart failure and is associated with increased rehospitalization and mortality compared with patients who have normal diuretic response

  • Impaired absorption, decreased renal blood flow, azotaemia, hypoalbuminaemia, and proteinuria result in reduced levels of active diuretics in the tubular lumen, and diminish diuretic effectiveness

  • Several treatment strategies, including increased dose of intravenous loop diuretics, combination therapy, and ultrafiltration, aim to improve biological availability of the drugs and counteract maladaptive responses in diuretic-resistant patients

  • Quantitative measures of diuretic response have been proposed, but need to be validated in larger populations of patients with acute heart failure

  • An enhanced understanding of diuretic response should ultimately lead to improved individualized approaches to treating patients with acute heart failure

Abstract

The administration of loop diuretics to achieve decongestion is the cornerstone of therapy for acute heart failure. Unfortunately, impaired response to diuretics is common in these patients and associated with adverse outcomes. Diuretic resistance is thought to result from a complex interplay between cardiac and renal dysfunction, and specific renal adaptation and escape mechanisms, such as neurohormonal activation and the braking phenomenon. However, our understanding of diuretic response in patients with acute heart failure is still limited and a uniform definition is lacking. Three objective methods to evaluate diuretic response have been introduced, which all suggest that diuretic response should be determined based on the effect of diuretic dose administered. Several strategies have been proposed to overcome diuretic resistance, including combination therapy and ultrafiltration, but prospective studies in patients who are truly unresponsive to diuretics are lacking. An enhanced understanding of diuretic response should ultimately lead to an improved, individualized approach to treating patients with acute heart failure.

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Figure 1: Diuretic therapy.
Figure 2: Mechanisms of loop diuretic resistance.
Figure 3: An approach to treating patients with acute heart failure who are diuretic resistant.

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Authors and Affiliations

  1. Department of Cardiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, Groningen, 9713 GZ, Netherlands

    Jozine M. ter Maaten, Mattia A. E. Valente, Kevin Damman, Hans L. Hillege & Adriaan A. Voors

  2. Department of Nephrology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, Groningen, 9713 GZ, Netherlands

    Gerjan Navis

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Contributions

J.M.t.M. and M.A.E.V. researched data for the article and wrote the manuscript. All authors made substantial contribution to discussion of the content, reviewed, and edited the manuscript before submission.

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Correspondence to Adriaan A. Voors.

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The authors declare no competing financial interests.

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ter Maaten, J., Valente, M., Damman, K. et al. Diuretic response in acute heart failure—pathophysiology, evaluation, and therapy. Nat Rev Cardiol 12, 184–192 (2015). https://doi.org/10.1038/nrcardio.2014.215

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