Kidney Transplantation in Acute Kidney Injury Research: Rodent Models, Mechanisms, and Interventional Strategies

Kidney transplantation is the optimal treatment for end-stage kidney disease (ESKD), but transplant-associated acute kidney injury (AKI), primarily driven by ischemia–reperfusion injury (IRI), contributes to delayed graft function (DGF) and inferior long-term graft outcomes. Rodent kidney transplantation models provide a clinically relevant platform. This review summarizes the establishment and application of rat and mouse kidney transplantation models for studying transplant-associated acute kidney injury. It highlights critical variables in model design, including surgical techniques, ischemic conditions, organ preservation, donor characteristics, and immunological settings that influence experimental outcomes. It further synthesizes current mechanistic evidence on oxidative stress, microvascular injury, immune activation, regulated cell death, tissue repair and fibrosis, molecular regulatory networks, multi-omics analyses, and remote organ injury. The review also examines interventions targeting donor conditioning, organ preservation and perfusion, reperfusion inflammation, recipient therapy, and regenerative repair, while considering their experimental limitations and translational relevance. Rodent kidney transplantation models can bridge conventional renal ischemia–reperfusion models and clinical transplantation. Future progress will depend on standardized surgical procedure, clinically relevant model selection, rigorous long-term outcome assessment, and the integration of emerging molecular technologies to enhance translational relevance.