Medical Science: Updates and Prospects Vol. 12

Kidney transplantation remains the gold-standard treatment for end-stage kidney disease (ESKD), conferring superior long-term survival, quality of life, and cost-effectiveness over maintenance dialysis. Despite substantial advances in immunosuppressive pharmacology, perioperative care, and organ preservation technology, ischemia-reperfusion injury (IRI) persists as a fundamental pathophysiological challenge in deceased-donor transplantation. Conventional preservation strategies — including static cold storage (SCS), hypothermic machine perfusion (HMP), and normothermic machine perfusion (NMP) — reduce but do not eliminate ischemic injury, thereby contributing to delayed graft function (DGF), immunological sensitization, and chronic allograft dysfunction. Ischemia-free kidney transplantation (IFKT) has emerged as a conceptually novel preservation approach aimed at maintaining uninterrupted normothermic oxygenated perfusion across all three phases of transplantation: donor procurement, ex vivo preservation, and recipient implantation. The first human case, reported by He and colleagues in 2019, demonstrated proof-of-concept feasibility with immediate graft function and absent dialysis requirement in a brain-dead donor pair. The first retrospective comparative cohort study, published by Yu and colleagues in 2024, reported comparable one-year patient and graft survival between IFKT and conventional kidney transplantation (CKT) in six donor pairs, though DGF occurred in one pair in both treatment arms (Yu et al., 2024). Concurrently, the landmark COPE randomised controlled trial demonstrated that one hour of end-ischemic NMP did not significantly reduce DGF in donation after circulatory death (DCD) kidneys compared with SCS alone, highlighting the importance of perfusion duration and timing. The NKP1 phase 1 cohort study confirmed the safety and feasibility of prolonged NMP up to 24 hours, with 100% 30-day graft survival and comparable 12-month estimated glomerular filtration rate (eGFR) to matched controls. This narrative review examines the conceptual basis, pathophysiological rationale, technical methodology, international protocols, clinical evidence, and future directions of IFKT, with careful alignment of conclusions to the current maturity of the evidence base. Potential advantages, substantiated limitations, and the substantial remaining evidence gaps — including the absence of multicentre randomised trial data, long-term outcomes, health-economic analyses, and DCD applicability — are critically discussed. Future directions in perfusion technology, biomarker-guided viability assessment, and therapeutic organ reconditioning are presented as investigational rather than established clinical practices.