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Mineralocorticoid Receptor Antagonists in Diabetic Kidney Disease

Daiji Kawanami1, Yuichi Takashi1, Yoshimi Muta1

  • 1Department of Endocrinology and Diabetes Mellitus, Fukuoka University School of Medicine, Fukuoka, Japan.

Frontiers in Pharmacology
|November 18, 2021
PubMed

Insights

Mineralocorticoid receptor antagonists (MRAs) show promise in treating diabetic kidney disease (DKD). Nonsteroidal MRAs offer improved selectivity and safety profiles compared to older steroidal options, particularly regarding hyperkalemia risk.

Area of Science:

  • Nephrology
  • Endocrinology
  • Pharmacology

Background:

  • Diabetic kidney disease (DKD) is a leading cause of end-stage kidney disease (ESKD).
  • Overactivation of the mineralocorticoid receptor (MR) contributes to kidney inflammation and fibrosis in diabetic conditions.
  • Existing steroidal MR antagonists (MRAs) like spironolactone and eplerenone have shown clinical benefits but raise concerns about selectivity and hyperkalemia.

Purpose of the Study:

  • To review current knowledge on MR antagonists (MRAs) for diabetic kidney disease (DKD) treatment.
  • To discuss the advantages of novel nonsteroidal MRAs.
  • To explore future perspectives for MRAs in managing DKD.

Main Methods:

  • Review of preclinical and clinical studies on MR and MRAs in DKD.
  • Analysis of the mechanisms of action of steroidal and nonsteroidal MRAs.
  • Evaluation of safety and efficacy data, focusing on hyperkalemia risk.

Main Results:

  • Preclinical data confirm MR's role in promoting DKD via inflammatory and fibrotic pathways.
  • Clinical studies support the efficacy of MRAs in DKD.
  • Nonsteroidal MRAs, such as finerenone, demonstrate high selectivity, potent anti-inflammatory/anti-fibrotic effects, and a lower risk of hyperkalemia.

Conclusions:

  • Mineralocorticoid receptor antagonists represent a promising therapeutic strategy for diabetic kidney disease.
  • Nonsteroidal MRAs offer a potentially safer and more effective alternative to steroidal agents.
  • Further research and clinical application of nonsteroidal MRAs are warranted for DKD management.
Keywords:
aldosteronediabetic kidney diseasediabetic nephropathymineralocorticoid receptor (MR)mineralocorticoid receptor antagonist (MRA)

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