Normothermic ex vivo kidney perfusion for graft quality assessment prior to transplantation

Abstract

Normothermic ex vivo kidney perfusion (NEVKP) represents a novel approach for graft preservation and functional improvement in kidney transplantation. We investigated whether NEVKP also allows graft quality assessment before transplantation. Kidneys from 30-kg pigs were recovered in a model of heart-beating donation (group A) after 30 minutes (group B) or 60 minutes (group C) (n = 5/group) of warm ischemia. After 8 hours of NEVKP, contralateral kidneys were resected, grafts were autotransplanted, and the pigs were followed for 3 days. After transplantation, renal function measured based on peak serum creatinine differed significantly among groups (P < .05). Throughout NEVKP, intrarenal resistance was lowest in group A and highest in group C (P < .05). intrarenal resistance at the initiation of NEVKP correlated with postoperative renal function (P < .001 at NEVKP hour 1). Markers of acid-base homeostasis (pH, HCO , base excess) differed among groups (P < .05) and correlated with posttransplantation renal function (P < .001 for pH at NEVKP hour 1). Similarly, lactate and aspartate aminotransferase were lowest in noninjured grafts versus donation after circulatory death kidneys (P < .05) and correlated with posttransplantation kidney function (P < .001 for lactate at NEVKP hour 1). In conclusion, assessment of perfusion characteristics and clinically available perfusate biomarkers during NEVKP allows the prediction of posttransplantation graft function. Thus, NEVKP might allow decision-making regarding whether grafts are suitable for transplantation.

Kidney Perfusion as an Organ Quality Assessment Tool—Are We Counting Our Chickens Before They Have Hatched?

“…The same group showed that kidney assessment during warm perfusion might lead to transplantation of initially discarded DCD kidneys [49]. Extending normothermic perfusion to longer periods (2 to 8 hours) has been explored in pig studies [50][51][52][53][54]. Kidneys not suitable for transplantation have been normothermically perfused for 24 hours, making use of urine recirculation, though not transplanted [55].…”

“…The kidney quality score is detailed below ( Table 1). Biomarkers determined in the perfusate of pig kidneys undergoing 8 hours of normothermic perfusion after exposure to 0, 30, or 60 minutes of warm ischemia showed that markers of acid-base homeostasis (pH, HCO3-, base excess) correlated with posttransplant renal function [50]. Similarly, lactate and AST were lowest in non-injured grafts and levels correlated with posttransplantat kidney function [50].…”

“…Different vasodilators or combinations of them (verapamil, epoprostenol, glyceril trinitrate, endothelin-1 antagonist, etc.) with various acting mechanisms have been added to organ perfusion circuits [50,55]. Whether one of these is superior in the setting of kidney perfusion is unknown; however, in normothermic liver perfusion, endotheline-1 antagonist or verapamil resulted in higher hepatic flows and lower AST levels [126].…”

The efficacy of HBOC‐201 in ex situ gradual rewarming kidney perfusion in a rat model

“…Machine perfusion has been developed as an alternative preservation method to cold storage (CS) with promising results in organ quality improvement . Different perfusion protocols have been studied by many groups and among the emerged perfusion protocols, normothermic machine perfusion has gained more attention as it provides the feasibility of assessing organ viability and function before transplant . It has also been shown that gradual rewarming from hypothermic to normothermic is superior to sudden normothermic perfusion after CS .…”

“…[3][4][5] Different perfusion protocols have been studied by many groups and among the emerged perfusion protocols, normothermic machine perfusion has gained more attention as it provides the feasibility of assessing organ viability and function before transplant. 6,7 It has also been shown that gradual rewarming from hypothermic to normothermic is superior to sudden normothermic perfusion after CS. 4,8 Although gradual rewarming solves the problem strategically, it remains to be established whether there is a need for oxygen carrier during gradual rewarming for providing a sufficient amount of oxygen.…”