Nonsteroidal mineralocorticoid receptor blockers as a new tool for managing cardiorenal risks in type 2 diabetes mellitus

Abstract

Today, the importance of targeted cardionephroprotection is increasingly increasing as one of the vectors of a multifactorial therapeutic strategy to reduce the risk of development and progression of complications of type 2 diabetes. Pathological hyperactivation of the renin-angiotensin-aldosterone system (RAAS) and mineralocorticoid receptors (MCRs) is considered as one of the mechanisms for the development of cadiorenal syndrome (RCS) in diabetes. Blocking this pathophysiological pathway in patients with CKD and type 2 diabetes can break the vicious circle of mutually aggravating damage to the kidneys and heart. ACE inhibitors and angiotensin receptor blockers (ARBs) are currently the standard of care in patients with CRS due to diabetes. But despite their effectiveness, the residual risk of CKD progression within 4–5 years remains high in almost half of patients with type 2 diabetes, mainly due to multicomponent processes of MCR hyperactivation. This causes a range of pathological reactions affecting the entire body and may contribute to kidney, heart and CD disease in patients with type 2 diabetes by promoting inflammation and fibrosis. Functional and structural changes in the kidneys and heart develop, which leads to the development of metabolic disorders, arterial hypertension, cardiovascular complications and progressive CKD. Pharmacological blockade of aldosterone binding to MCR appears to be an effective additional line for preventing the progression of the pathological cascade of KRS reactions in type 2 diabetes. The recently developed selective non-steroidal MCR antagonist (nsAMPR) finerenone has convincingly demonstrated improved renal and cardiovascular outcomes in patients with CKD and type 2 diabetes. This review covers in detail the role of MCRs in the development of cardiorenal syndrome in type 2 diabetes and CKD, describes the mechanisms of effectiveness of MCR blockade in preventing the progression of cardiorenal syndrome in type 2 diabetes and the difference between non-steroidal MCRs and steroids, and presents the results of RCTs confirming the cardionephroprotective potential of nsAMCRs in CKD and diabetes. type 2, and the place of finerenone as a multifactorial therapeutic strategy for type 2 diabetes in clinical practice.