Molecular Mechanisms and Emerging Therapeutic Targets in Diabetic Nephropathy: An Updated Review

Abstract

Diabetic nephropathy (DN), a common and severe complication of diabetes, is the leading cause of end-stage kidney disease (ESKD). The present review is to explore the underlying mechanisms, molecular signaling pathways, biomarkers, therapeutic targets, and interventional strategies involved in DN. Chronic hyperglycemia induces metabolic and hemodynamic disturbances that promote oxidative stress, inflammation and fibrosis through key pathways such as the polyol pathway, advanced glycation end-products (AGEs), protein kinase C (PKC) and the renin-angiotensin-aldosterone system (RAAS). Biomarkers including albuminuria, serum creatinine, TGF-β, IL-6, and KIM-1 are valuable for early diagnosis and disease monitoring. Targeting ANG-II, AGE’s and PKC forms the basis for multiple treatment strategies along with combination therapies particularly sodium-glucose cotransporter-2 (SGLT2) inhibitors and RAAS blockers offering superior outcomes. Additionally, emerging interventions like dietary modulation and cell-based therapies hold therapeutic potential. A multifaceted, early-intervention approach is crucial for effective DN management and slowing disease progression.