Yuliya Lytvyn1, Lucas C Godoy2,3, Rosalie A Scholtes4, Daniël H van Raalte4, David Z Cherney5,6,7. 1. Toronto General Hospital Research Institute, UHN, 585 University Ave, 8N-845, Toronto, Ontario, M5G 2N2, Canada. julia.lytvyn@mail.utoronto.ca. 2. Peter Munk Cardiac Centre, University of Toronto, Toronto, Canada. 3. Instituto do Coracao (InCor), Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil. 4. Diabetes Center, Department of Internal Medicine, Amsterdam University Medical Center, location VU University Medical Center, Amsterdam, The Netherlands. 5. Department of Medicine, Division of Nephrology, University Health Network, University of Toronto, Toronto, Canada. 6. Banting and Best Diabetes Centre, Toronto, Canada. 7. Department of Physiology, University of Toronto, Toronto, Canada.
Abstract
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. RECENT FINDINGS: 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.
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. RECENT FINDINGS: 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.
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Authors: Yuliya Lytvyn; Petter Bjornstad; Daniel H van Raalte; Hiddo L Heerspink; David Z I Cherney Journal: Endocr Rev Date: 2020-04-01 Impact factor: 19.871