Mineralocorticoid receptor antagonists: Efficacy and safety in chronic kidney disease

The mineralocorticoid receptor (MR) has a multifaceted role in normal physiologic functions. However, research has uncovered the deleterious consequences of overactivation of the MR. It has been implicated in chronic kidney disease (CKD) via its strong association with glomerulosclerosis, interstitial fibrosis, proteinuria, and decline in glomerular filtration rate, as well as in cardiovascular diseases through mechanisms such as excessive extracellular matrix accumulation, oxidative stress, haemodynamic changes, and sustained inflammation. As such, efforts have poured into developing therapeutic agents to inhibit the detrimental effects of MR overactivation. This narrative review describes the background to elucidating the role of MR overactivation in CKD associated with diabetes, followed by an overview of the clinical development history of MR antagonists (MRAs), initially steroidal, followed by agents with non-steroidal structure. Clinical trials have demonstrated antiproteinuric effects of both MRA classes; however, only the non-steroidal class has shown reductions in major adverse kidney events, with finerenone being the most widely studied. Both MRA classes also benefit heart failure and hypertension, common comorbidities in CKD, though steroidal MRAs have shown greater antihypertensive effects as well as greater risk for hyperkalaemia. This review also highlights guideline recommendations that have been developed to incorporate the latest clinical evidence, along with practical ways to manage hyperkalaemia with MRA use.