Optimizing Prolonged (6 h) Normothermic Machine Perfusion of Donor Kidneys (PROPER Study)

Ex situ normothermic machine perfusion (NMP) holds great promise in preserving and concomitantly evaluating the viability of kidney grafts. NMP for 1 to 2 h has been shown to be feasible and safe, demonstrating no adverse impact on early graft function. Prolonging the duration of NMP offers an extended timeframe for evaluation, besides creating a window for pretransplant therapeutical interventions. This study aimed to assess the feasibility of extending the duration of perfusion to 6 h.

We investigated the prerequisites to extend the warm perfusion of donor kidneys safely for up to 6 h. Human donor kidneys deemed unsuitable for transplantation were included for experimental NMP. Throughout the perfusion process, we assessed metabolic activity, as well as the extent of biochemical, hemolytic, and histological injury through biopsy, urine, and perfusate analyses. Stepwise alterations were made to the protocol accordingly.

An analysis of 30 discarded kidneys revealed that improvements in erythrocyte quality, oncotic pressure, and correction of electrolyte imbalances facilitated the achievement of steady flow volumes and ensured a favorable macroscopic appearance of the graft. Extending the perfusion period to 6 h displayed preserved renal viability and stable histological characteristics.

The presented protocol shows prolonging NMP of donor kidneys to 6 h is feasible. We have implemented pivotal elements including the use of fresh (≤ 7 days) washed red blood cells, the addition of albumin, and urine recirculation, resulting in a stable and balanced perfusion. Ongoing refinements are necessary to enable the clinical application of a more prolonged NMP.