Decrease of renal resistance during hypothermic oxygenated machine perfusion is associated with early allograft function in extended criteria donation kidney transplantation

Abstract

Hypothermic oxygenated machine perfusion (HOPE) was recently tested in preclinical trials in kidney transplantation (KT). Here we investigate the effects of HOPE on extended-criteria-donation (ECD) kidney allografts (KA). Fifteen ECD-KA were submitted to 152 ± 92 min of end-ischemic HOPE and were compared to a matched group undergoing conventional-cold-storage (CCS) KT (n = 30). Primary (delayed graft function-DGF) and secondary (e.g. postoperative complications, perfusion parameters) endpoints were analyzed within 6-months follow-up. There was no difference in the development of DGF between the HOPE and CCS groups (53% vs. 33%, respectively; p = 0.197). Serum urea was lower following HOPE compared to CCS (p = 0.003), whereas the CCS group displayed lower serum creatinine and higher eGFR rates on postoperative days (POD) 7 and 14. The relative decrease of renal vascular resistance (RR) following HOPE showed a significant inverse association with serum creatinine on POD1 (r = − 0.682; p = 0.006) as well as with serum urea and eGFR. Besides, the relative RR decrease was more prominent in KA with primary function when compared to KA with DGF (p = 0.013). Here we provide clinical evidence on HOPE in ECD-KT after brain death donation. Relative RR may be a useful predictive marker for KA function. Further validation in randomized controlled trials is warranted. Trial registration: clinicaltrials.gov (NCT03378817, Date of first registration: 20/12/2017).

Advances in Hypothermic and Normothermic Perfusion in Kidney Transplantation

“…The effects of end ischaemic oxygenated HMP was trialled in ECD kidneys and compared to ECD kidneys undergoing SCS. No significant difference in DGF incidence was observed between group [65].…”

“…The value of using renal resistance to predict transplant outcomes was also demonstrated recently in an oxygenated HMP study. The percentage fall in renal resistance was found to be inversely correlated to serum creatinine on day 1 and 2 after transplant, indicating a functional link between an individual kidney's response to perfusion during storage and graft function [65]. Patients who receive a kidney that exhibited high resistance during the first hour of HMP have higher post-operative serum creatinine at 1 year and a higher incidence of DGF immediately post-transplant [74].…”

Renal Delivery of Pharmacologic Agents During Machine Perfusion to Prevent Ischaemia-Reperfusion Injury: From Murine Model to Clinical Trials

“…Despite oxygen consumption is significantly decreased in hypothermic condition (at 4-10°C), there is still an important cellular metabolism. The technique of HOPE (Hypothermic Oxygenated Machine Perfusion) has been recently recognized as a powerful tool in preservation technologies for the additional value to oxygenate perfusate at a partial pressure of 60-100 kPa (146)(147)(148). In rodent and pig models, pre-treatment of ischemic grafts with HOPE appeared able to counteract endothelial dysfunction, macrophage activation and improved mitochondrial metabolic pathways (149)(150)(151)(152)(153).…”

“…In rodent and pig models, pre-treatment of ischemic grafts with HOPE appeared able to counteract endothelial dysfunction, macrophage activation and improved mitochondrial metabolic pathways (149)(150)(151)(152)(153). Furthermore, preliminary clinical experience as well as retrospective studies started to compare incidence in DGF and other renal function parameters in HOPE treated graft versus conventional SCS kidneys (147,154).…”

“…Similarly, in a prospective case-matched pilot study, Meister FA. et al demonstrated the safety and feasibility of HOPE in human ECD grafts, finding a decrease in renal resistance as central predictor of allograft function (147). However, no significant differences were assessed in DGF incidence.…”