Role and application prospective of non-steroidal MRA in the treatment of diabetic kidney disease.

Abstract

Chronic kidney disease (CKD) has diverse etiologies and complex pathogenesis, and is prone to recurrent episodes and prolonged illness. In recent years, the prevalence of CKD has been increasing year by year, and the global prevalence in the general population has reached 14.3%. Diabetic kidney disease (DKD) is a common complication of diabetes mellitus (DM), and about 20-40% of DM patients have combined DKD, which is also the main cause of CKD and end-stage renal disease (ESRD). DM catalyzes CKD in approximately 30-50% of global cases, affecting around 285 million individuals. It primarily triggers diabetic nephropathy (DN), the leading cause of end-stage renal disease worldwide. Research indicates that activation of the mineralocorticoid receptor (MR) plays a role in the onset and progression of DKD. Counteracting MR overactivation offers antioxidative, anti-inflammatory, and anti-fibrotic benefits, thereby ameliorating target organ damage. MR antagonists (MRAs) such as spironolactone and eplerenone have been validated for renal protection. However, their clinical application is hindered by adverse effects including hyperkalemia, gynecomastia in males, erectile dysfunction, and menstrual irregularities in females. Finerenone, a novel non-steroidal MRA, exhibits a unique mechanism of action, binding to MR and inhibiting the recruitment of transcription co-factors involved in gene expression, effectively slowing the progression of diabetic nephropathy (DN). In addition, finerenone demonstrates improved safety and efficacy in treating heart failure and chronic kidney disease. It also plays a significant role in the management of atrial fibrillation and myocardial infarction. This article reviews recent studies on finerenone, summarizing its mechanism of action in treating DN, evidence from clinical trials, adverse reactions, combined use with other inhibitors, and future prospective, aiming to provide insights for the prevention and treatment of DN.