Hypothermia for expanded criteria organ donors in kidney transplantation in France (HYPOREME): a multicentre, randomised controlled trial.

ABSTRACT

BACKGROUND: Expanded criteria donors help to increase graft availability, but provide organs with an increased risk of delayed graft function. We aimed to investigate whether donor hypothermia decreases the risk of delayed graft function compared with normothermia. METHODS: We did this multicentre, randomised, controlled, parallel-arm trial at 53 intensive care units and transplant centres in France. We included expanded criteria donors in whom death was diagnosed based on neurological criteria, in compliance with French law, and the recipients of their kidney grafts. Eligible expanded criteria donors were older than 60 years or were aged 50-59 years and had at least two other risk factors (history of hypertension, creatinine >132 µmol/L, or cerebrovascular cause of death). Donors were randomly assigned to hypothermia (34-35°C) or normothermia (36·5-37·5°C). Machine perfusion was used routinely. Randomisation was done using a computer-generated, interactive, web-response system, in permuted blocks (block size six), stratified by centre. Outcome assessors were masked; investigator masking was not feasible. The primary outcome was the proportion of kidney recipients with delayed graft function, defined as renal replacement therapy within 7 days after transplantation, assessed in the modified intention-to-treat (mITT) population, which included all recipients who received at least one kidney from an expanded criteria donor, with the exception of those under guardianship. Secondary outcomes in expanded criteria donors were the number of organs recovered and transplanted, kidney function, body temperature, total volume of fluids administered, blood pressure and need for vasopressors and inotropes, and adverse events (cardiovascular events, metabolic disturbances, and coagulation disorders). Secondary outcomes in kidney recipients were duration of hospital stay, kidney graft function and vital status at day 7, day 28, 3 months, and 1 year after transplantation, and adverse events (infections, cardiovascular events, and surgical complications). Secondary outcomes were assessed in the mITT population. The trial was registered at ClinicalTrials.gov, NCT03098706. FINDINGS: Between Nov 9, 2017, and March 3, 2021, 365 donors were randomly assigned, of whom 298 (151 [51%] male, 147 [49%] female) provided kidneys to 526 recipients (323 [61%] male, 203 [39%] female). 251 recipients in the hypothermia group and 275 recipients in the normothermia group were included in the analysis. Graft function was delayed in 40 (16%) of 251 recipients in the hypothermia group and 58 (21%) of 275 recipients in the normothermia group (odds ratio 0·71 [95% CI 0·44-1·13]; p=0·14; absolute difference -5·2% [95% CI 11·8-1·5]). Compared with donors in the normothermia group, donors in the hypothermia group had higher highest mean arterial pressure (115 mm Hg [SD 22] vs 108 mm Hg [20]; p=0·001). 1 year after transplantation, recipients in the hypothermia group had a lower mean creatinine concentration (152·4 µmol/L [SD 59·1] vs 169·7 µmol/L [51·4]; p=0·0351) and a higher mean creatinine clearance (42·3 mL/min/1·73 m2 [15·8] vs 40·5 mL/min/1·73 m2 [17·9]; p=0·0414) than those in the normothermia group. No significant differences between groups were identified for any other secondary outcomes. INTERPRETATION: Hypothermia in expanded criteria donors whose organs were routinely stored using machine perfusion did not decrease the frequency of delayed kidney graft function. However, hypothermia was associated with a lower serum creatinine concentration and a higher creatinine clearance 1 year after transplantation. FUNDING: French Ministry of Health and French Intensive Care Society.