Cell death in kidney transplantation: Mechanisms and therapeutic perspectives

Kidney transplantation is the optimal therapy for end-stage renal disease, yet long-term graft survival remains limited by ischemia-reperfusion injury, rejection, and chronic allograft dysfunction. Accumulating evidence indicates that multiple regulated cell death pathways-including apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagy-are critically involved in transplant injury. These pathways interact extensively, shaping the immune microenvironment, amplifying inflammation, and influencing graft fate. Emerging forms of cell death, such as cuproptosis, parthanatos, and NETosis, further expand the mechanistic landscape of transplant pathology. This review summarizes current mechanistic insights and experimental and clinical evidence linking regulated cell death to kidney transplant outcomes, and discusses therapeutic strategies targeting cell death pathways. Integrating cell death modulation into precision medicine may provide novel avenues to improve graft survival and patient prognosis.