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.