Hypothermic machine perfusion prevents hyperacute graft loss in pig-to-primate kidney xenotransplantation after 5-hours of cold Ischemia.

BACKGROUND: Xenotransplantation (XTx) is a promising strategy to address the organ shortage. Clinical application will likely require off-site procurement from designated pathogen-free (DPF) facilities, introducing unavoidable cold ischemic time (CIT). The impact of CIT and organ preservation method on graft function in XTx remains unclear. METHODS: We evaluated eight cases of pig-to-baboon kidney xenotransplantation performed after five hours of CIT, comparing static cold storage (SCS) to hypothermic machine perfusion (HMP) preservation. Outcomes were assessed relative to six additional pig-to-baboon transplants performed with minimal CIT. RESULTS: All grafts preserved with SCS experience hyperacute rejection within 90 min of reperfusion, even in recipients with low levels of preformed anti-pig antibodies. In contrast, all HMP-preserved grafts reperfuse without clinical evidence of injury and maintain function for more than 14 days. Grafts transplanted with minimal CIT show similarly favorable outcomes. CONCLUSIONS: Porcine kidneys are highly sensitive to ischemia-reperfusion injury after cold preservation across xenogeneic barriers. Routine SCS leads to early graft failure, while HMP mitigates ischemic injury and may enable successful clinical XTx despite prolonged CIT.