Exosomes in diabetic kidney disease: pathogenesis, biomarker discovery, and emerging therapeutics-a comprehensive systematic review.

Diabetic kidney disease (DKD), characterized by progressive renal dysfunction, is a prevalent microvascular complication of diabetes mellitus and a leading cause of end-stage renal disease worldwide. Despite advances in glycemic and blood pressure control, the incidence and prevalence of DKD continue to escalate, posing a growing public health challenge. Extracellular vesicles, particularly exosomes, are nanometer-sized vesicles secreted by diverse cells and have emerged as key regulators of intercellular communication. By transferring molecular cargo-including proteins, lipids, and nucleic acids-they exert pleiotropic effects on cellular homeostasis and participate in both physiological and pathological processes. Accumulating evidence has revealed dynamic alterations in the quantity and composition of urinary exosomes under diabetic conditions, implicating these vesicles in the multifactorial pathogenesis of DKD and highlighting their promise as liquid biopsy biomarkers for DKD. This review provides a comprehensive overview of the landscape of research on exosomes in DKD. We elucidate their roles in molecular pathology, investigate their potential for diagnostic and prognostic biomarker discovery powered by multi-omics and machine learning approaches, and examine their implications for therapeutic applications, including their use as drug delivery vehicles and direct therapeutic agents. Looking forward, we highlight critical research gaps and future directions, emphasizing the need for artificial intelligence (AI)-integrated multi-omics analyses to decipher exosome heterogeneity, large-scale multicenter trials to validate biomarker efficacy, and innovative strategies to overcome barriers in clinical translation, ultimately paving the way for personalized medicine in DKD management.