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Aldosterone: effects on the kidney and cardiovascular system

Nature Reviews Nephrology volume 6, pages 261–273 (2010)Cite this article

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Abstract

Aldosterone, a steroid hormone with mineralocorticoid activity, is mainly recognized for its action on sodium reabsorption in the distal nephron of the kidney, which is mediated by the epithelial sodium channel (ENaC). Beyond this well-known action, however, aldosterone exerts other effects on the kidney, blood vessels and the heart, which can have pathophysiological consequences, particularly in the presence of a high salt intake. Aldosterone is implicated in renal inflammatory and fibrotic processes, as well as in podocyte injury and mesangial cell proliferation. In the cardiovascular system, aldosterone has specific hypertrophic and fibrotic effects and can alter endothelial function. Several lines of evidence support the existence of crosstalk between aldosterone and angiotensin II in vascular smooth muscle cells. The deleterious effects of aldosterone on the cardiovascular system require concomitant pathophysiological conditions such as a high salt diet, increased oxidative stress, or inflammation. Large interventional trials have confirmed the benefits of adding mineralocorticoid-receptor antagonists to standard therapy, in particular to angiotensin-converting-enzyme inhibitor and angiotensin II receptor blocker therapy, in patients with heart failure. Small interventional studies in patients with chronic kidney disease have shown promising results, with a significant reduction of proteinuria associated with aldosterone antagonism, but large interventional trials that test the efficacy and safety of mineralocorticoid-receptor antagonists in chronic kidney disease are needed.

Key Points

  • Beyond its role in the regulation of renal sodium reabsorption in the distal nephron, aldosterone may exert deleterious effects on the kidney and the cardiovascular system particularly in the presence of a high-salt diet

  • Aldosterone induces inflammation, fibrosis, mesangial cell proliferation and podocyte injury in the kidney

  • Aldosterone contributes to cardiovascular remodeling and fibrosis in animals on a high-salt diet

  • Large clinical trials have demonstrated the efficacy of mineralocorticoid-receptor antagonists in patients with heart failure

  • Despite encouraging results from small interventional studies, large interventional studies in patients with chronic kidney disease are needed to test the efficacy and safety of mineralocorticoid-receptor antagonists

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Figure 1: Regulation of ENaC by aldosterone.
Figure 2: Mechanisms of aldosterone-induced kidney injury.
Figure 3: Synergistic effects of aldosterone and Ang II in vascular smooth muscle cells.

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Acknowledgements

The authors' work described in this Review was supported by the Canadian Institutes of Health Research (CIHR) grants 37917 and 82790, a Canada Research Chair (CRC) on Hypertension and Vascular Research from the CIHR/CRC Program of the Government of Canada, and the Canada Fund for Innovation (all to E. L. S.). M. B. was supported by the Heart and Stroke Foundation of Canada.

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  1. Department of Medicine, Sir Mortimer B. Davis–Jewish General Hospital and Lady Davis Institute for Medical Research, McGill University, 3755 Côte-Ste-Catherine Road, Montreal, H3T 1E2, QC, Canada

    Marie Briet & Ernesto L. Schiffrin

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Correspondence to Ernesto L. Schiffrin.

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E. L. Schiffrin receives grant/research support from the Canadian Institutes of Health Research and receives grant/research support from and is a consultant for Pfizer Canada. M. Briet declares no competing interests.

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Briet, M., Schiffrin, E. Aldosterone: effects on the kidney and cardiovascular system. Nat Rev Nephrol 6, 261–273 (2010). https://doi.org/10.1038/nrneph.2010.30

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