Prolonged ex-vivo normothermic machine perfusion for kidney regeneration

Chronic kidney disease is a debilitating condition with a poor quality of life. Dialysis offers little improvement in this medical condition which carries a mortality rate that surpasses most cancers. Dialysis is one of the most expensive treatments, putting pressure on the sustainability of the health care system. Currently kidney transplantation is the only viable option for patients with kidney failure to regain quality of life and health. The number of organs available for transplantation is insufficient with a widening gap between supply and demand. Nowadays, centers accept older and higher risk donor organs with co-morbidity, often leading to non-function, complications and with half of the patients back on dialysis within 15 years. Furthermore, many donor kidneys have to be discarded as too damaged and beyond repair. Increasing the quality and therefore transplantability of these high-risk donor organs could significantly increase the donor kidney pool.
We would like to introduce and clinically evaluate prolonged normothermic machine perfusion (PNMP) to challenge this situation. Using prolonged normothermic perfusion of marginal donor organs, we aim to kick
start regeneration in the kidney before transplantation, improving function and survival long-term. Furthermore, the choice to accept or decline a donor kidney organ is currently based on subjective criteria and causes great uncertainty amongst clinicians. There is a dire need for tools to aid in decision making and reduce this uncertainty. Biomarkers predictive of graft regeneration are lacking. Samples from perfused kidneys and donor recipients will be collected and analysed to allow the formulation of a kidney fitness index.

Prolonged normothermic machine perfusion (PNMP) can be used to ex-vivo regenerate marginal donor organs, resulting in increased kidney graft viability and survival of the transplanted organ.

1 year

Eligible and consenting patients who will receive a donor kidney will be included for participation in this study. Current practice is to preserve donor kidneys on hypothermic machine perfusion (HMP). In this study, donor kidneys (n=18) will be taken off the HMP after arrival in the transplant center. These will then be perfused with oxygenated perfusate using the NMP device following an optimised NMP protocol. First, a cohort of DCD kidneys (n=6) will be subjected to 1 hour of NMP and subsequently transplanted [NMP1]. Before extending the duration, secondary endpoints will be evaluated. Thereafter, the duration of NMP will be prolonged to 3 hours (n=6) [PNMP3] and consequently 6 hours (n=6) [PNMP6].