The interplay between endothelial cell dysfunction and podocyte injury in diabetic nephropathy: a comprehensive review of current evidence.

Diabetic nephropathy (DN) remains the leading cause of end-stage renal disease globally. Emerging evidence highlights the bidirectional crosstalk between glomerular endothelial cell (GEC) dysfunction and podocyte injury as a key driver of DN progression. This review synthesizes current understanding of the molecular mechanisms, clinical correlations, and therapeutic strategies targeting this interplay. Mechanistically, hyperglycemia-induced oxidative stress, dysregulated angiogenesis, and aberrant extracellular vesicle (EV)-mediated signaling contribute to a self-perpetuating cycle of glomerular injury. Clinically, biomarkers of endothelial-podocyte axis disruption predict disease progression and therapeutic response. Novel therapies, including endothelin receptor antagonists, sodium-glucose cotransporter 2 (SGLT2) inhibitors, and mesenchymal stem cell derived EVs, show promise for restoring glomerular filtration barrier (GFB) integrity. This review integrates multi-omics insights to propose a unified model of DN pathogenesis and precision medicine approaches.