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Mechanisms of Disease: the role of aldosterone in kidney damage and clinical benefits of its blockade

Abstract

In the past 10 years, many widely accepted concepts relating to aldosterone production and its pathogenetic role have changed. We now know that aldosterone is produced not only by the zona glomerulosa of the adrenal cortex, but also in the heart, blood vessels, kidney and brain; such extra-epithelial production occurs mainly during tissue repair. Also, increased aldosterone levels contribute to vessel inflammation, oxidative stress, endothelial dysfunction and organ damage. As such, aldosterone has a key role in the development of myocardial fibrosis. Anti-aldosterone treatment has proven effective in patients with heart failure. Experimental evidence regarding the role of aldosterone in kidney damage has accumulated. Aldosterone infusion can counteract the beneficial effects of treatment with angiotensin-converting-enzyme inhibitors, causing more-severe proteinuria and an increased number of vascular and glomerular lesions; treatment with aldosterone antagonists can reverse these alterations. Preliminary observations in pilot studies in humans confirm the experimental findings, supporting the hypothesis that aldosterone antagonists are renoprotective in clinical practice. Studies in larger populations with longer follow-up are needed to confirm this theory.

Key Points

  • Experimental evidence supports a role for systemic and locally produced aldosterone in kidney damage that is independent of renin and angiotensin II

  • Pathophysiological effects of aldosterone include development of extracellular matrix and fibrosis, inflammation, stimulation of reactive oxygen species production, endothelial dysfunction, and cell growth and proliferation

  • Clinical studies performed to date, although being primarily small, open-label trials with short follow-up, have shown a marked antiproteinuric effect of the aldosterone antagonist spironolactone that is independent of blood pressure changes

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Correspondence to Lucia Del Vecchio.

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Vecchio, L., Procaccio, M., Viganò, S. et al. Mechanisms of Disease: the role of aldosterone in kidney damage and clinical benefits of its blockade. Nat Rev Nephrol 3, 42–49 (2007). https://doi.org/10.1038/ncpneph0362

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