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Finerenone: a New Mineralocorticoid Receptor Antagonist Without Hyperkalemia: an Opportunity in Patients with CKD?

  • Therapeutic Trials (M Weir, Section Editor)
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Abstract

Aldosterone binds to the mineralocorticoid receptor and has an important regulatory role in body fluid and electrolyte balance. It also influences a variety of different cell functions such as oxidative stress, inflammation and organ fibrosis. The important role of the tissue-specific mineralocorticoid receptors in cardiovascular and renal injury has been shown in knockout animals and in clinical studies Mineralocorticoid receptor antagonists seem to exert their beneficial effects via anti-oxidative, anti-inflammatory and anti-fibrotic effects. Spironolactone and eplerenone were the first steroidal mineralocorticoid receptor antagonist. The established steroidal mineralocorticoid receptor antagonists show important therapeutic effects but are hampered by a variety of side effects, most importantly clinically significant hyperkaliemia. Selective non-steroidal mineralocorticoid receptor antagonists have been recently developed and demonstrate effectiveness in early clinical trials. Finereroneholds promise for the future application of this new mineralocorticoid receptor antagonist class in patients with chronic kidney disease since it has shown a significant reduction in UACR combined with a safety profile similar to that in the placebo group. However, further long-term studies investigating relevant clinical end points like reduction in cardiovascular or renal event rate are warranted.

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  1. Klinik für Nieren- und Hochdruckerkrankungen, Medizinische Hochschule Hannover MHH, Hannover, Germany

    Hermann Haller, Anna Bertram, Klaus Stahl & Jan Menne

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  1. Hermann Haller
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Correspondence to Hermann Haller.

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Drs. Haller, Bertram, Stahl, and Menne declare no conflicts of interest.

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Key points

• Although the established physiological function of the renal mineralocorticoid receptor is regulation of sodium reabsorption and potassium excretion, activation of the mineralocorticoid receptor in extra-renal tissues also contributes to the pathogenesis of cardiovascular injury.

• The important role of the tissue-specific mineralocorticoid receptors in cardiovascular and renal injury has been shown in knockout animals and in clinical studies.

• The established steroidal mineralocorticoid receptor antagonists show important therapeutic effects but are hampered by a variety of side effects, most importantly clinically significant hyperkaliemia, which limits their use especially in patients with chronic kidney disease and reduced glomerular filtration rates.

• Selective non-steroidal mineralocorticoid receptor antagonists have been recently developed and demonstrate effectiveness in early clinical trials.

• The significant reduction in UACR in patients receiving finerenone, combined with a safety profile similar to that in the placebo group, holds promise for the future application of this new mineralocorticoid receptor antagonist class in patients with chronic kidney disease. However, further long-term studies investigating relevant clinical end points like reduction in cardiovascular or renal event rate are warranted.

This article is part of the Topical Collection on Therapeutic Trials

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Haller, H., Bertram, A., Stahl, K. et al. Finerenone: a New Mineralocorticoid Receptor Antagonist Without Hyperkalemia: an Opportunity in Patients with CKD?. Curr Hypertens Rep 18, 41 (2016). https://doi.org/10.1007/s11906-016-0649-2

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