Urinary exosomes in diabetic kidney disease: Pathophysiological insights and diagnostic potential

Exosomes are nanosized extracellular vesicles (30-150 nm) secreted by most cell types, carrying various biomolecules that reflect the physiological or pathological state of their cells of origin. Owing to their molecular diversity and stability in bodily fluids, exosomes have emerged as promising tools in precision medicine. Diabetic kidney disease (DKD), affecting approximately 30-40% of individuals with diabetes, remains the leading cause of end-stage kidney disease worldwide. Current diagnostic tools, including albuminuria and estimated glomerular filtration rate, lack sensitivity and specificity for early detection and dynamic monitoring of disease activity. Emerging evidence indicates that urinary exosomes derived from glomerular cells, particularly podocytes, provide an insight into intrarenal pathobiology, reflecting real-time cellular injury and key disease-associated changes. Given the central role of podocytes in maintaining the glomerular filtration barrier and their early involvement in DKD, podocyte-derived urinary exosomes hold potential and may enable earlier intervention and more personalized therapeutic strategies. Beyond their biomarker potential, exosomal protein and microRNA cargo such as Regucalcin, Elf3, PHYD1, miR-155, miR-21, miR-29, actively participate in key pathogenic processes, including inflammation, fibrosis, oxidative stress, and metabolic dysregulation, thereby contributing to DKD progression. This review synthesizes current evidence providing mechanistic insights on urinary exosomes and their cargo as emerging biomarkers in DKD, highlighting their translational potential in advancing precision nephrology. In addition, we also discuss the current challenges in clinical implementation of exosome-based biomarkers into routine clinical practice for the diagnosis of DKD.