Novel Organ Perfusion and Preservation Strategies in Transplantation – where are we going in the UK?

This review article focuses on current clinical outcomes with novel perfusion strategies in organ transplantation. Broadly, these approaches can be divided into in-situ regional perfusion in the donor and ex-situ machine perfusion of individual organs. In both settings hypothermic and normothermic techniques are in clinical use. Evidence from full text articles, abstracts and data presented at scientific meetings has been considered. Animal studies have been excluded. The review focuses on kidney, liver, pancreas, heart and lungs. The level of evidence ranges from quasi-experimental work in human pancreas to multiple meta-analyses of Randomised Controlled Trials for hypothermic machine perfusion of kidneys. The data in this review was presented to experts in organ perfusion and preservation at the National Health Service Blood and Transplant Preservation and Perfusion Future Strategy Summit in London in October 2018. The outcomes of the meeting are discussed in the review after due consideration of the available evidence base.

Introduction

Rising demand for organs for transplantation has led to increased utilisation of grafts from donors that fall outside standard acceptance criteria, which are perceived as higher-risk donors. Static cold storage (SCS) may be adequate for organs from so-called ‘standard-criteria’ donors but is insufficient for the preservation of organs from older donors and/or those with a higher-risk of graft failure. SCS therefore doesn’t facilitate the expansion of organ acceptance criteria for transplantation and likely compounds ongoing organ shortage 1. There has been an explosion of novel strategies to perfuse, preserve, repair and resuscitate organs prior to transplantation 2. Technological advances have supported the development of these strategies with a number of devices entering clinical practice or trials. Broadly speaking the focus of strategies has been either the donor with in-situ regional perfusion, or the transport and pre-implantation phase with ex-situ machine perfusion of isolated organs. Although no universal nomenclature is in use, in the context of deceased organ donation ex-situ is the preferred terminology over ex-vivo given that machine perfusion occurs after the organs have been removed from the body of a deceased donor 3. A number of perfusion variables including temperature, oxygen delivery and perfusate (blood-based, blood analogues or specifically designed media) are currently being investigated 2. The theoretical advantages of these dynamic perfusion and preservation modalities have translated into encouraging results that appear to suggest an increased graft utilisation, the ability to undertake assessment of graft viability prior to transplantation, with a potentially improved outcome for recipients 4. However, the increasing number of devices available combined with the wide range of regimens of perfusion technology make the choice increasingly complex. Whilst current trials focus on demonstrating the clinical benefit of individual strategies, the time has come to establish how best to tailor the techniques to specific donor types and conditions while defining their role for each organ, accounting for donor- and organ-specific risk factors.

This review undertakes a horizon scan of the clinical outcomes reported to date using various novel perfusion strategies applied in organ transplantation. The data (Figure 1, Appendix 1) was presented to experts at the National Health Service Blood and Transplant (NHSBT) Preservation and Perfusion Future Strategy Summit in London in October 2018. The outcomes of the meeting are discussed later after due consideration of the available evidence.