A Single-center, Pilot, Prospective, Randomized Clinical Study of Hypothermic Oxygenated Perfusion With or Without Adsorption in Histologically Evaluated Kidneys Retrieved From Marginal Donors

In recent years, growing interest has been addressed to the use of dynamic preservation of the kidneys as a tool to improve graft function and survival. Retrospective analyses and a randomized controlled trial showed that pre-transplant machine perfusion (MP) is associated with a lower incidence of delayed graft function (DGF) and improved one-year graft survival as compared with static cold storage. However, the overall beneficial effect of MP on transplant outcomes is largely driven by treatment effect in recipients of grafts from marginal donors.

Hypothermic oxygenated perfusion has been found to reduce early allograft injury and to improve post-transplant outcomes in a randomized controlled trial of liver transplantation from older donors. In vitro studies show that perfusion reduces endothelial damage to the sinusoidal capillaries and increases adenosine triphosphate production. As far as kidney transplantation is concerned, little data is available on the outcomes of grafts treated with perfusion. In rat models of allogeneic kidney transplant, perfusion-treated grafts displayed better short-term function, less tubular injury, fewer interstitial infiltrates of immune cells and milder endothelial activation than the untreated counterparts.

MP is not only beneficial per se. It can also be exploited as a means to deliver additional treatment to the graft. For instance, there is in vivo evidence that hemoadsorption improves renal blood flow during perfusion and reduces the release of cytokines and prostaglandins at reperfusion in a porcine model of kidney transplantation. Beneficial effects of hemoadsorption have been documented in the setting of continuous renal replacement treatment for septic shock. In the setting of pre-transplant organ conditioning, cytokine adsorption paired to normothermic perfusion has been found to reduce inflammatory gene expression and increase oxidative phosphorylation pathway gene expression in human kidneys. Whether adsorption paired to perfusion reduces the inflammatory response and whether this is of clinical relevance in transplantation of histologically evaluated kidneys from marginal donors, is worth investigating.