Mineralocorticoid Antagonism and Diabetic Kidney Disease
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Purpose of Review
Type 2 diabetes (T2D) is associated with an increased risk of diabetic kidney disease (DKD), cardiovascular disease, and heart failure, in part through activation of the renin-angiotensin-aldosterone system (RAAS). Although recent cardiovascular outcome trials have identified newer therapeutic agents such as sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1)-receptor agonists that reduce the risk of these complications, patients still exhibit residual cardiorenal morbidity and mortality. Accordingly, the identification of pharmacological agents that attenuate micro- and macrovascular complications related to T2D is a major priority. Our aim was to review evidence for the role of novel mineralocorticoid receptor antagonists (MRAs) that are being developed as adjunctive therapies to reduce the risk of DKD and cardiovascular disease in the setting of T2D.
Dual RAAS blockade with angiotensin-converting enzyme (ACE) inhibitor plus angiotensin receptor blockade (ARB) or ARB plus renin inhibition increases serious adverse events such as acute kidney injury and stroke. Due to the potential for these serious side effects, more recent interest has focused on newer, more selective non-steroidal MRAs such as finerenone as cardiorenal protective therapies. Finerenone reduces albuminuria in the setting of DKD in patients with T2D and has a lower risk of hyperkalemia compared to currently available MRAs.
Novel MRAs such as finerenone have the potential to reduce the risk of DKD progression in patients with T2D. The impact of finerenone on hard, long-term cardiorenal endpoints is being examined in the FIGARO and FIDELIO trials in patients with DKD.
KeywordsMineralocorticoid receptor antagonist Diabetes Diabetic kidney disease
Y.L. is the corresponding author for the manuscript. All authors contributed to the design and drafting the paper and reviewed and approved the manuscript for scholarly content.
Y.L. is supported by a Canadian Diabetes Association (Diabetes Canada) Fellowship. D.V.R. is supported by fellowships of the Dutch Diabetes Foundation and Marie Curie – European Union. D.Z.I.C. receives support from the Canadian Institutes of Health Research, as well as Diabetes Action Canada, a Strategy for Patient-Oriented Research initiative supported by the Canadian Institutes for Health Research. D.Z.I.C. also receives operating funding from the Heart and Stroke Richard Lewar Centre of Excellence in Cardiovascular Research and Banting and Best Diabetes Centre, University of Toronto. D.Z.I.C. is the recipient of the University of Toronto, Department of Medicine Merit Award. The authors were fully responsible for all content and editorial decisions were involved at all stages of manuscript development and have approved the final version.
Compliance with Ethical Standards
Conflict of Interest
Yuliya Lytvyn, Lucas C. Godoy, and Rosalie A. Scholtes declare that they have no conflict of interest.
Daniël H. van Raalte receives research funding from AstraZeneca, Boehringer Ingelheim, Merck, and Sanofi. He has received consulting fees and/or speaking honoraria from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck, and Sanofi. All honoraria are directly transferred to the employer (AUMC).
David Z. Cherney receives operating funds from Boehringer Ingelheim, Janssen, AstraZeneca, and Merck. He has received consulting fees and/or speaking honoraria from Boehringer Ingelheim, Janssen, AstraZeneca, Merck, Mitsubishi-Tanabe, Sanofi, Bayer, Prometic, and Abbvie.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
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