Potential Role of Mineralocorticoid Receptor Antagonists in Nondiabetic Chronic Kidney Disease and Glomerular Disease

Abstract

Glomerular disease is a leading cause of chronic kidney disease (CKD) and end-stage kidney disease. Although diabetic kidney disease is the most common cause of glomerular disease, non-diabetic causes include malignancy, systemic autoimmune conditions, drug effects, or genetic conditions. Nondiabetic glomerular diseases are rare diseases, with a paucity of high-quality clinical trials in this area. Furthermore, late referral can result in poor patient outcomes. This manuscript reviews the current management of nondiabetic glomerular disease and explores the latest developments in drug treatment in this area. Current treatment of nondiabetic glomerular disease aims to manage complications (edema, hypertension, proteinuria, hyperlipidemia, hypercoagulability, and thrombosis) as well as target the underlying cause of glomerular disease. Treatment options include renin-angiotensin-aldosterone system inhibitors, statins/non-statin alternatives, loop diuretics, anticoagulation agents, immunosuppressives, and lifestyle and dietary modifications. Effective treatment of nondiabetic glomerular disease is limited by heterogeneity and a lack of understanding of the disease pathogenesis. Sodium-glucose cotransporter-2 inhibitors and nonsteroidal mineralocorticoid receptor antagonists (ns-MRAs, such as finerenone), with their broad anti-inflammatory and antifibrotic effects, have emerged as valuable therapeutic options for a range of cardiorenal conditions, including CKD. ns-MRAs are an evolving drug class of particular interest for the future treatment of nondiabetic glomerular disease, and there is evidence that these agents may improve kidney prognosis in various subgroups of patients with CKD. The benefits offered by ns-MRAs may present an opportunity to reduce the progression of CKD from a spectrum of glomerular disease. Several novel ns-MRA are in clinical development for both diabetic and nondiabetic CKD.