Strategies to improve function of marginal grafts and to recover discharged grafts in liver and kidney transplantation

The discrepancy between the number of transplant procedures and the patients in waiting list is linked to the scarcity of suitable donors. Dynamic perfusion of marginal grafts seems to be promising in their recovery. Twenty discarded kidneys were used to perform a preclinical study with a new hypothermic oxygenate machine perfusion. Encouraging preclinical results allowed us to perform a clinical trial, in whom 10 extended criteria donors (ECD) livers and 10 ECD kidneys were perfused with the new machine and then transplanted, and compared with control groups (30 ECD liver transplant and 30 ECD kidney transplant preserved in cold storage). Overall graft dysfunction was 10% in study groups, compared to 31.6% in control group (P < 0.001). The peak of aspartate aminotransferase within 7-days post liver transplant was 637 U/L in control group compared to 344 U/L of liver study group (P = 0.006). Patients receiving a kidney graft with more than 2 hours of hypothermic oxygenate perfusion treatment had lower rate of delayed graft function than control group (0% vs. 40%, p = 0.04). Preclinical analyses demonstrated the absence of damage at histological examination, the improved metabolic activity and a diminished expression of genes related to ischemia/reperfusion injury, especially in case of hyperbarism application during perfusion. Further studies are needed to confirm this hypothesis. On the other hand, the clinical phase of present study documented the safety and efficacy of a new type of machine perfusion, which is low-cost and, unlike the already present in commerce, was effective and safe in both liver and kidney transplantation settings.