Sense and Sensibilities of Organ Perfusion as a Kidney and Liver Viability Assessment Platform

Abstract

Predicting organ viability before transplantation remains one of the most challenging and ambitious objectives in transplant surgery. Waitlist mortality is high while transplantable organs are discarded. Currently, around 20% of deceased donor kidneys and livers are discarded because of “poor organ quality”, Decisions to discard are still mainly a subjective judgement since there are only limited reliable tools predictive of outcome available. Organ perfusion technology has been posed as a platform for pre-transplant organ viability assessment. Markers of graft injury and function as well as perfusion parameters have been investigated as possible viability markers during ex-situ hypothermic and normothermic perfusion. We provide an overview of the available evidence for the use of kidney and liver perfusion as a tool to predict posttransplant outcomes. Although evidence shows post-transplant outcomes can be predicted by both injury markers and perfusion parameters during hypothermic kidney perfusion, the predictive accuracy is too low to warrant clinical decision making based upon these parameters alone. In liver, further evidence on the usefulness of hypothermic perfusion as a predictive tool is needed. Normothermic perfusion, during which the organ remains fully metabolically active, seems a more promising platform for true viability assessment. Although we do not yet fully understand “on-pump” organ behaviour at normothermia, initial data in kidney and liver are promising. Besides the need for well-designed (registry) studies to advance the field, the catch-22 of selection bias in clinical studies needs addressing.

Extracellular vesicles in kidney disease

“…Machine perfusion of donor kidneys before transplantation could improve organ preservation and reduce ischaemic injury, potentially resulting in improved graft function. In addition, this strategy might enable organ quality and viability to be improved before transplantation, potentially increasing the donor pool 118 . Addition of extracellular vesicles to the perfusion solution could be an innovative strategy for delivering pro-regenerative molecules to the graft before transplantation (Fig.…”

Unraveling metabolism during kidney perfusion using tracer studies: a systematic review

“…Initial clinical experience with a short period of normothermic perfusion to ‘resuscitate’ the kidney following static cold storage shows feasibility and the results of a first large randomized controlled trial are awaited 16–19 . As the kidney is metabolically active at normothermic temperatures, it is believed that this platform is better suited for viability assessment and resuscitation compared to hypothermic perfusion 5,11 . Nevertheless, no validated viability markers in kidney have been identified, unlike for liver where more evidence is available 4,11 …”

“…5,11 Nevertheless, no validated viability markers in kidney have been identified, unlike for liver where more evidence is available. 4,11 As the kidney remains metabolically active during both hypothermic and normothermic perfusion, it needs adequate metabolic support and it is surprising how little we know about the kidney's metabolic behavior during perfusion. 20 Furthermore, changes of the metabolome might also correlate with post-transplant outcomes and as such serve as viability markers.…”

Advances in Normothermic Machine Perfusion of the Kidney: Evidence for Clinical Practice and Underlying Mechanistic Actions

“…NMP can also be used to assess viability and as a platform for the administration of therapies directly to the kidney to aid regeneration and repair. These topics have been reviewed in several recent publications [27][28][29][30][31][32][33] . This review focuses on the application of NMP in kidney transplantation, detailing the clinical evidence and examining the underlying mechanistic actions.…”