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Mineralocorticoid Receptor Antagonism in Chronic Kidney Disease

Panagiotis I Georgianos1, Rajiv Agarwal2

  • 1Section of Nephrology and Hypertension, 1st Department of Medicine, AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Kidney International Reports
|September 13, 2021
PubMed

Insights

Mineralocorticoid receptor (MR) overactivation drives chronic kidney disease (CKD) progression. Blocking MR with finerenone, a novel nonsteroidal antagonist, shows improved cardiorenal outcomes in patients with CKD and type 2 diabetes.

Area of Science:

  • Nephrology
  • Cardiology
  • Pharmacology

Background:

  • Mineralocorticoid receptor (MR) overactivation in chronic kidney disease (CKD) exacerbates sodium retention, hypertension, inflammation, and fibrosis, contributing to cardiorenal disease progression.
  • MR blockade is a therapeutic strategy to slow CKD progression and reduce cardiovascular events.
  • Steroidal MR antagonists like spironolactone and eplerenone have limitations.

Purpose of the Study:

  • To review the safety and efficacy of steroidal MR antagonists (spironolactone, eplerenone) in CKD.
  • To describe the mechanism of action of finerenone, a novel nonsteroidal MR antagonist (MRA).
  • To discuss finerenone's potential as a therapeutic option for improving clinical outcomes in CKD patients.

Main Methods:

  • Review of existing literature on steroidal MRAs in CKD.
  • Analysis of preclinical data comparing finerenone to steroidal MRAs in animal models.
  • Examination of Phase II and III clinical trial data for finerenone in patients with type 2 diabetes and heart/kidney disease.

Main Results:

  • Finerenone demonstrated a superior benefit/risk profile compared to steroidal MRAs in preclinical CKD models.
  • Phase II trials indicated finerenone offers benefits exceeding risks in patients with type 2 diabetes and cardiorenal disease.
  • A Phase III trial showed finerenone significantly improved kidney failure and cardiovascular outcomes in CKD patients with type 2 diabetes compared to placebo.

Conclusions:

  • Finerenone represents a novel nonsteroidal MRA with a distinct mechanism of action.
  • Finerenone shows promise for improving cardiorenal outcomes in patients with CKD, particularly those with type 2 diabetes.
  • The data support finerenone as a valuable therapeutic option in managing CKD progression and associated cardiovascular risks.
Keywords:
chronic kidney diseaseeplerenonefinerenonemineralocorticoid receptorspironolactone

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