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Considerations for the future: current and future treatment paradigms with mineralocorticoid receptor

Murray Epstein1

  • 1Division of Nephrology and Hypertension, University of Miami Miller School of Medicine, Miami, Florida, USA.

Kidney International Supplements
|May 9, 2022
PubMed

Insights

Finerenone, a mineralocorticoid receptor antagonist, shows promise for kidney and cardiovascular protection beyond diabetes. Future trials will explore its efficacy in nondiabetic chronic kidney disease and its interaction with FGF23 and Klotho.

Area of Science:

  • Nephrology
  • Cardiology
  • Endocrinology

Background:

  • Mineralocorticoid receptor (MR) overactivation contributes to inflammation and fibrosis in chronic kidney disease (CKD).
  • Finerenone, a nonsteroidal MR antagonist, has demonstrated kidney and cardiovascular benefits in patients with type 2 diabetes and CKD.

Purpose of the Study:

  • To explore the potential efficacy of finerenone in patients with nondiabetic CKD.
  • To investigate the role of MR activation in nondiabetic kidney disease pathogenesis.
  • To examine the interrelationship between fibroblast growth factor 23 (FGF23), Klotho, and aldosterone in CKD.

Main Methods:

  • Initiation of the FIND-CKD clinical trial (NCT05047263) to test finerenone in nondiabetic CKD.
  • Establishment of the FIONA clinical development program for finerenone in pediatric CKD.
  • Proposed future investigations into the FGF23-Klotho-aldosterone axis in CKD.

Main Results:

  • Successful demonstrations of finerenone's efficacy in diabetic CKD provide a basis for further research.
  • The pathogenetic role of MR activation is hypothesized to extend to nondiabetic kidney disease.

Conclusions:

  • MR antagonism therapy is proposed to be effective in nondiabetic CKD.
  • Further research into the FGF23-Klotho-aldosterone axis may reveal novel therapeutic targets for CKD.
  • Finerenone represents a potential therapeutic strategy for a broader CKD population.
Keywords:
Klothochronic kidney diseasefibroblast growth factor 23 (FGF23)renin–angiotensin systemsickle cell disease (SCD)–related nephropathy

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