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The incidence and implications of aldosterone breakthrough

Nature Clinical Practice Nephrology volume 3, pages 486–492 (2007)Cite this article

Abstract

Interruption of the renin–angiotensin–aldosterone system has become a leading therapeutic strategy in the treatment of chronic heart and kidney disease. Angiotensin-converting-enzyme inhibitors and angiotensin-receptor blockers do not, however, uniformly suppress the renin–angiotensin–aldosterone system. Plasma aldosterone levels are elevated in a subset of patients despite therapy. This phenomenon, known as 'aldosterone escape' or 'aldosterone breakthrough', has only been directly examined in small numbers of patients. The key questions of how often breakthrough occurs and whether breakthrough leads to worse outcomes have yet to be definitively answered. In this Review, we summarize the reported data on the incidence and clinical implications of aldosterone breakthrough, and highlight areas of uncertainty that have yet to be adequately addressed in the literature. Although the available evidence is not strong enough to support widespread screening for aldosterone breakthrough, our findings should prompt physicians to consider the phenomenon in select patients as well as guide future research efforts.

Key Points

  • Serum aldosterone levels are increased in a subset of patients treated with angiotensin-converting-enzyme inhibitors and/or angiotensin-receptor blockers, a phenomenon known as 'aldosterone breakthrough'

  • A small number of studies indicate that the incidence of aldosterone breakthrough is between 10% and 53%

  • The wide range in the reported incidence of breakthrough is probably attributable to the use of different definitions, and to comorbidity status

  • Aldosterone breakthrough could be associated with left ventricular hypertrophy, decreased exercise capacity, and higher rates of urinary albumin excretion

  • Clinicians should consider testing for aldosterone breakthrough in patients with refractory heart or kidney disease despite maximal therapeutic blockade of the renin–angiotensin–aldosterone system

  • Breakthrough detected in the setting of stable potassium and salt balance could warrant the addition of aldosterone antagonists or renin inhibitors to conventional heart and kidney failure regimens

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Figure 1: Process by which studies were selected for inclusion in this Review

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Acknowledgements

Désirée Lie, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape-accredited continuing medical education activity associated with this article.

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Authors and Affiliations

  1. AS Bomback is Doc J Thurston III Fellow in the Division of Nephrology and Hypertension, and a Renal Epidemiology Fellow in the Department of Epidemiology, and PJ Klemmer is Professor of Medicine in the Division of Nephrology and Hypertension, School of Medicine, School of Public Health, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.,

    Andrew S Bomback & Philip J Klemmer

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Correspondence to Andrew S Bomback.

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Bomback, A., Klemmer, P. The incidence and implications of aldosterone breakthrough. Nat Rev Nephrol 3, 486–492 (2007). https://doi.org/10.1038/ncpneph0575

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