Mitigating Risk of Aldosterone in Diabetic Kidney Disease

Overview

Journal Curr Opin Nephrol Hypertens

Specialties Cardiology & Vascular Diseases
Nephrology

Date 2019 Oct 11

PMID 31599747

Citations 13

Authors

Marie Frimodt-Moller

Frederik Persson

Peter Rossing

Affiliations

Soon will be listed here.

Abstract

Purpose Of Review: Diabetic kidney disease is a growing problem leading to end-stage kidney disease but also atherosclerotic cardiovascular disease and heart failure. Aldosterone is a key risk factor promoting inflammation and fibrosis causing cardio-renal failure. Current options and challenges with mitigating the risk of aldosterone are reviewed.

Recent Findings: More aggressive renin-angiotensin-aldosterone system (RAAS) blockade can be maintained in individuals with hyperkalemia if new potassium binders are added. Aldosterone synthase inhibitors may lower aldosterone without causing hyperkalemia. Novel nonsteroidal mineralocorticoid receptor antagonists (MRA) are able to lower proteinuria and markers of heart failure, with limited potassium problems and without renal impairment. Ongoing clinical trials are evaluating the safety and potential benefits of nonsteroidal MRAs on progression of renal disease and development of cardiovascular outcomes in type 2 diabetes and kidney disease.

Summary: Aldosterone is an important driver of inflammation and fibrosis leading to renal and cardiovascular complications. MRA lower albuminuria but data showing prevention of end-stage kidney disease are lacking. Side effects including hyperkalemia have previously prevented long-term studies in diabetic kidney disease but new treatment strategies with potassium binders, aldosterone synthase inhibitors and nonsteroidal MRA have been developed for clinical testing.

Citing Articles

Phase 1 studies of the safety, tolerability, pharmacokinetics, and pharmacodynamics of BI 690517 (vicadrostat), a novel aldosterone synthase inhibitor, in healthy male volunteers.

Schulze F, Schaible J, Goettel M, Tanaka Y, Hohl K, Schultz A Naunyn Schmiedebergs Arch Pharmacol. 2025; .

PMID: 39899058 DOI: 10.1007/s00210-025-03838-0.

Dysregulation of the 3β-hydroxysteroid dehydrogenase type 2 enzyme and steroid hormone biosynthesis in chronic kidney disease.

Zuo Y, Zha D, Zhang Y, Yang W, Jiang J, Wang K Front Endocrinol (Lausanne). 2024; 15:1358124.

PMID: 39525849 PMC: 11543464. DOI: 10.3389/fendo.2024.1358124.

Combination therapy for kidney disease in people with diabetes mellitus.

van Raalte D, Bjornstad P, Cherney D, de Boer I, Fioretto P, Gordin D Nat Rev Nephrol. 2024; 20(7):433-446.

PMID: 38570632 DOI: 10.1038/s41581-024-00827-z.

Aldosterone, Methylglyoxal, and Glycated Albumin Interaction with Macrophage Cells Affects Their Viability, Activation, and Differentiation.

Zambre S, Bangar N, Mistry A, Katarmal P, Khan M, Ahmed I ACS Omega. 2024; 9(10):11848-11859.

PMID: 38497023 PMC: 10938338. DOI: 10.1021/acsomega.3c09420.

Finerenone: Questions and Answers-The Four Fundamental Arguments on the New-Born Promising Non-Steroidal Mineralocorticoid Receptor Antagonist.

Di Lullo L, Lavalle C, Scatena A, Mariani M, Ronco C, Bellasi A J Clin Med. 2023; 12(12).

PMID: 37373685 PMC: 10299719. DOI: 10.3390/jcm12123992.

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