Pathogenesis and Therapeutic Perspectives of Tubular Injury in Diabetic Kidney Disease: An Update.

Abstract

Diabetic kidney disease (DKD), a well-characterized microvascular complication associated with the progression of diabetes mellitus, has been identified as the leading etiological factor contributing to the global burden of end-stage kidney disease (ESKD). Historically, DKD research has predominantly centered on glomerular mechanisms; however, recent studies have increasingly emphasized the critical role of tubular dysfunction. Extensive evidence has elucidated the key pathological drivers of tubular injury in DKD, encompassing metabolic dysregulation, pro-inflammatory signaling pathways, diverse cellular stress responses, and epithelial-mesenchymal transition (EMT). Furthermore, emerging mechanistic studies reveal that autophagic flux impairment and epigenetic memory formation collaboratively drive cellular senescence in DKD. Regarding the treatment of DKD, various hypoglycemic drugs, as well as hypotensive drugs, and microcirculatory improvers have garnered significant attention. Recently, stem cell-based interventions and precision gene editing techniques have unveiled novel therapeutic paradigms for DKD, fundamentally expanding the treatment arsenal beyond conventional pharmacotherapy. This review synthesizes updated insights into the pathogenesis of tubular injury in DKD and highlights promising therapeutic strategies for managing this condition.