Molecular mechanisms and novel therapeutic targets of diabetic kidney disease.

Diabetic kidney disease (DKD) remains a leading cause of end-stage renal disease worldwide, characterized by increasing prevalence and limited therapeutic options. This review comprehensively synthesizes recent advances in the molecular mechanisms underlying DKD progression, focusing on key cellular events including podocyte injury, tubular damage, endothelial dysfunction, pericyte loss, and immune-inflammatory responses that drive glomerular and tubulointerstitial fibrosis. We further elaborate on critical pathways such as lipotoxicity, mitochondrial dysfunction and oxidative stress, aberrant autophagy, inflammasome activation, and profibrotic signaling. The review also highlights clinically approved agents including renin-angiotensin-aldosterone system inhibitor, sodium-glucose cotransporter 2 inhibitors, endothelin receptor antagonists, mineralocorticoid receptor antagonists, glucagon-like peptide-1 receptor agonists, and emerging therapeutic targets and agents currently under preclinical and clinical investigation, including anti-inflammatory, anti-fibrotic, and metabolic interventions. By integrating mechanistic insights with translational evidence, this work aims to provide a comprehensive review for the development of DKD.