Clinical perspective—evolving evidence of mineralocorticoid receptor antagonists in patients with chronic kidney disease and type 2 diabetes

Abstract

Chronic kidney disease (CKD) in type 2 diabetes is a large and growing problem leading to end-stage kidney disease, atherosclerotic cardiovascular disease, and heart failure (HF). Aldosterone is a key risk factor in promoting inflammation and fibrosis, which causes cardiorenal failure. Treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers does not prevent overactivation of the mineralocorticoid receptor. Therapeutic options and challenges with blocking MR overactivation by aldosterone are reviewed herein. Whereas classic steroidal mineralocorticoid receptor antagonists (MRAs) reduced albuminuria in short-term studies of diabetic and nondiabetic CKD, long-term studies evaluating hard endpoints such as loss of kidney function were not conducted in CKD because of side effects (primarily hyperkalemia). Novel nonsteroidal MRAs reduce proteinuria and markers of HF, with lower risk of hyperkalemia and without renal impairment, in comparison to steroidal MRAs. Furthermore, recent clinical trials have demonstrated the efficacy of the novel, selective, nonsteroidal MRA finerenone to delay progression of kidney and cardiovascular disease, including HF, in patients with CKD and type 2 diabetes. Concomitantly, the safety profile of finerenone is good, with few patients discontinuing treatment because of hyperkalemia, even among study participants with a low estimated glomerular filtration rate (>25 ml/min per 1.73 m²). Novel nonsteroidal MRAs such as finerenone hold the potential to be an attractive addition to the treatment paradigm in the management of patients with CKD and type 2 diabetes, targeting the unmet need of managing increased inflammation and fibrosis attributable to MR overactivation.