Endothelial Dysfunction in Diabetic Nephropathy: A Vascular Perspective on Renal Protection

Abstract

Diabetic nephropathy (DN), a leading cause of end-stage renal disease worldwide, is increasingly recognized as a disease of the microvasculature. Among the earliest pathophysiological events in DN is endothelial dysfunction, which plays a central role in the onset and progression of renal injury. This review presents a comprehensive overview of the molecular mechanisms linking hyperglycemia to endothelial dysfunction, with a focus on oxidative stress, inflammation, and impaired nitric oxide signaling. We further explore the roles of endothelial-derived mediators, glycocalyx degradation, and endothelial-to-mesenchymal transition (EndMT) in aggravating glomerular and peritubular capillary injury. Clinical implications, current diagnostic challenges, and potential biomarkers of endothelial injury are discussed. We highlight emerging therapeutic interventions targeting endothelial pathways, including pharmacological agents, lifestyle interventions, and advanced drug delivery systems. Understanding the vascular underpinnings of DN offers new insights into early diagnosis and renal protection, marking endothelial restoration as a pivotal strategy in managing diabetic kidney disease