Programmed Cell Death in Diabetic Kidney Disease: Mechanisms and Therapeutic Targeting.

The escalating incidence and mortality of diabetic kidney disease (DKD) underscore the critical need to elucidate its pathogenesis. Programmed cell death (PCD) plays a dual role in maintaining physiological homeostasis and driving pathological processes in DKD. Accumulating evidence demonstrates that apoptosis, autophagy, pyroptosis, and ferroptosis contribute directly or indirectly to DKD progression via distinct gene-regulated signaling pathways. Recently identified PCD modes (eg, necroptosis, parthanatos) remain poorly characterized in DKD, with emerging evidence suggesting crosstalk between different PCD pathways. This review synthesizes current knowledge on PCD-mediated DKD pathogenesis and PCD-targeted therapies, while highlighting research limitations (eg, unclear PCD interactions, translational gaps). We propose that dissecting the multifaceted roles of PCD in DKD will deepen mechanistic understanding and accelerate the development of novel therapeutics, offering significant scientific and clinical benefits.