Exploring Novel Therapeutic Approaches for Chronic Kidney Disease

Abstract

Chronic kidney disease (CKD) is a significant global health burden, affecting millions of individuals worldwide. Despite current treatment strategies focusing on glycemic control and renin-angiotensin system blockade, these approaches merely delay the progression to end-stage renal disease (ESRD) and are associated with potential adverse effects. Recent advancements in our understanding of the complex pathophysiology of CKD have unveiled various unique processes contributing to its development, including vascular alterations, podocyte and renal epithelial cell loss, matrix deposition, inflammation, and metabolic dysregulation. This comprehensive review critically evaluates novel therapeutic approaches targeting these distinct pathways implicated in CKD pathogenesis. Strategies discussed include endothelial glycocalyx restoration, endothelin receptor antagonists, anti-apoptotic and podocyte regeneration therapies, anti-inflammatory and antioxidant agents, sodium-glucose co-transporter 2 (SGLT2) inhibitors, mitochondria-targeted therapies, anti-fibrotic agents, and interventions targeting epithelial-to-mesenchymal transition (EMT). While preclinical studies have demonstrated promising results for many of these approaches, their translation to clinical settings has been challenging due to safety concerns, lack of efficacy in trials, and the heterogeneity of CKD pathogenesis. The review highlights the importance of identifying appropriate patient populations, developing precision medicine strategies, exploring combination therapies, and leveraging novel drug delivery systems and regenerative medicine approaches to overcome current obstacles and improve therapeutic outcomes for CKD patients