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BackgroundNormothermic machine perfusion (NMP) aims to reduce ischemia–reperfusion injury in donor livers and its clinical manifestation, early allograft dysfunction (EAD) by maintaining perfusion and oxygenation. However, there is limited data on which NMP perfusate biomarkers might be associated with such EAD and the role of perfusate hemoglobin has not been assessed.MethodsWe performed a pilot retrospective analysis of adult donor livers undergoing NMP between 2020 and 2022 at our center. NMP was commenced at the recipient hospital after initial static cold storage. All NMP circuits were primed in the same manner according to the manufacturer's instructions. Livers were stratified by initial perfusate hemoglobin below (≤5.2 mmol/L) or above (>5.2 mmol/L) the median. The association between hemoglobin levels and EAD or recipient peak transaminase levels was assessed.ResultsAmong 23 livers, eight were considered unsuitable for transplantation, leaving 15 livers for assessment. Higher initial hemoglobin was associated with a lower risk of EAD (0% vs. 55.6%, p = 0.04). Perfusate hemoglobin decreased after NMP initiation (p = 0.003) and negatively correlated with recipient peak transaminase levels (ALT: ρ = −0.72, p = 0.002; AST: ρ = −0.79, p < 0.001). Consistently, higher hemoglobin livers also demonstrated lower perfusate liver enzymes.ConclusionsPerfusate hemoglobin levels decreased during NMP, and lower perfusate hemoglobin levels were associated with a higher incidence of EAD and higher levels of liver injury markers. Maintaining higher hemoglobin levels during NMP may help reduce ischemia–reperfusion injury and prevent or attenuate EAD. Larger prospective studies are needed to validate the findings of this pilot study.
BackgroundNormothermic machine perfusion (NMP) aims to reduce ischemia–reperfusion injury in donor livers and its clinical manifestation, early allograft dysfunction (EAD) by maintaining perfusion and oxygenation. However, there is limited data on which NMP perfusate biomarkers might be associated with such EAD and the role of perfusate hemoglobin has not been assessed.MethodsWe performed a pilot retrospective analysis of adult donor livers undergoing NMP between 2020 and 2022 at our center. NMP was commenced at the recipient hospital after initial static cold storage. All NMP circuits were primed in the same manner according to the manufacturer's instructions. Livers were stratified by initial perfusate hemoglobin below (≤5.2 mmol/L) or above (>5.2 mmol/L) the median. The association between hemoglobin levels and EAD or recipient peak transaminase levels was assessed.ResultsAmong 23 livers, eight were considered unsuitable for transplantation, leaving 15 livers for assessment. Higher initial hemoglobin was associated with a lower risk of EAD (0% vs. 55.6%, p = 0.04). Perfusate hemoglobin decreased after NMP initiation (p = 0.003) and negatively correlated with recipient peak transaminase levels (ALT: ρ = −0.72, p = 0.002; AST: ρ = −0.79, p < 0.001). Consistently, higher hemoglobin livers also demonstrated lower perfusate liver enzymes.ConclusionsPerfusate hemoglobin levels decreased during NMP, and lower perfusate hemoglobin levels were associated with a higher incidence of EAD and higher levels of liver injury markers. Maintaining higher hemoglobin levels during NMP may help reduce ischemia–reperfusion injury and prevent or attenuate EAD. Larger prospective studies are needed to validate the findings of this pilot study.
Kidney transplantation is the preferred treatment for end-stage renal disease and is limited by donor organ availability. Normothermic Machine Perfusion (NMP) might facilitate safe transplantation of marginal organs. Previous clinical implementations have been limited to short perfusions. NKP1 was a single centre, phase 1, 36-patient, three-stage cohort study investigating the safety and feasibility of up to 24 hours of renal NMP prior to transplantation. We observed a 30-day graft survival of 100%, with comparable outcomes to a matched control cohort (12-month estimated glomerular filtration rate (eGFR) 46.3 vs 49.5mL/min/1.73m2, p=0.44) despite much longer total preservation times (15.7 vs 8.9 hours controls, p <0.0001). We saw strong correlations between biomarkers measured ex-situ and post-transplant outcomes, including graft function at one year (correlation between GST-Pi delta and 12-month eGFR, R=0.54, p=0.001). Renal NMP is useful for optimising logistics and as an organ assessment technique, and has potential to expand the donor pool. Trial registration number: ISRCTN13292277.
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