Understanding the Effects of nsMRA vs MRA

Management of chronic kidney disease among patients with type 2 diabetes has undergone significant change in the last decade. Once handcuffed by a lack of safe and efficacious options, changing standards of care coming as the result of pharmacotherapeutic advancement have ushered in a new era of management for this patient population.

This change has been spearheaded by 2 particular classes—a familiar face in the form of SGLT2 inhibitors and the novel nonsteroidal mineralocorticoid receptor antagonist (nsMRA) finerenone (Kerendia), which received approval in July 2021 for reducing the risk of sustained eGFR decline, kidney failure, cardiovascular death, non-fatal myocardial infarction, and hospitalization for heart failure in adult patients with chronic kidney disease associated with type 2 diabetes.

Finerenone first captivated the attention of nephrologists, endocrinologists, and other providers managing patients with type 2 diabetes with the release of data from the FIDELIO-DKD and FIGARO-DKD trials. The number of specialists captivated by the agent and its potential benefit grew with the release of data surrounding the cardiovascular benefits among patients with heart failure observed within the FINEARTS-HF trial at the European Society of Cardiology Congress 2024.

In this segment, which is part 2 of a 5-part series, discussants Edgar Lerma, MD, a nephrologist, and Anuradha Lala-Trindade, MD, a cardiologist, explore the unique features of finerenone as a nsMRA, contrasting it with traditional MRAs like spironolactone. Lala-Trindade highlights that finerenone's increased selectivity for the mineralocorticoid receptor and non-steroidal structure help reduce hormonal side effects common with other MRAs. Additionally, finerenone’s balanced distribution between cardiac and renal tissues may support its dual kidney and cardiovascular benefits, unlike spironolactone, which primarily benefits renal outcomes.

Lala-Trindade further explains finerenone's potential for anti-fibrotic and anti-inflammatory effects in both organs and suggests that its hyperkalemia risk may be more manageable in chronic kidney disease patients, making it a promising option in this population.

Discussants Background:

Edgar Lerma, MD, a clinical professor of Medicine in the Section of Nephrology at the University of Illinois at Chicago and a nephrologist with Associates In Nephrology based in Chicago.

Anuradha Lala-Trindade, MD, the director of Heart Failure Research, program director of the Advanced Heart Failure and Transplant Fellowship, and associate professor of Medicine at The Mount Sinai Fuster Heart Hospital & Department of Population Health Science and Policy.

Relevant disclosures for Lerma include Akebia, Astra Zeneca, Bayer, Boehringer Ingelheim, Glaxo Smith Kline, Otsuka, Travere, Vifor, and Fresenius. Relevant disclosures for Lala-Trindade include Merck, AstraZeneca, Cytokinetics, and Novartis.

References:

1. Campbell P. Finerenone (Kerendia) approved for chronic kidney disease associated with type 2 diabetes. HCP Live. July 9, 2021. Accessed October 23, 2024. https://www.hcplive.com/view/finerenone-kerendia-approved-chronic-kidney-disease-associated-with-type-2-diabetes.
2. Campbell P. FDA updates Finerenone label to reflect Cardiovascular Outcomes Data. HCP Live. September 8, 2022. Accessed October 23, 2024. https://www.hcplive.com/view/fda-updates-finerenone-label-to-reflect-cardiovascular-outcomes-data.
3. Solomon SD, McMurray JJV, Vaduganathan M, et al. Finerenone in Heart Failure with Mildly Reduced or Preserved Ejection Fraction. N Engl J Med. Published online September 1, 2024. doi:10.1056/NEJMoa2407107