Mild hypothermia for expanded criteria kidney donors: balancing evidence and uncertainty

Judicious use of kidneys from expanded criteria donors (defined as donors aged >60 years or aged 50–59 years with at least two other risk factors [history of hypertension, creatinine >132 μmol/L, or cerebrovascular cause of death]) dead by neurological criteria can substantially increase the pool of organs available for transplantation. Expanded criteria donors are an important source of organs in several countries worldwide, especially in contexts where kidney transplantation from living donors is infrequent. However, transplantation of kidneys from expanded criteria donors is associated with increased risk of delayed graft function (ie, the need for renal replacement therapy during the first week after transplantation), premature organ failure, acute rejection, and worse survival. In this scenario, a key unmet need and research priority emerges: to improve the value of kidney transplantation from expanded criteria donors. Achieving high value for patients (defined as a higher ratio of good outcomes to cost) is the overarching goal of health-care delivery, a goal that is important for patients and unites the interests of all stakeholders in the health-care system. If value for patients improves, the economic sustainability of the health-care system increases. Various strategies have been implemented to address this priority for kidney transplantation, including machine perfusion techniques, pre-implantation donor kidney biopsy, and therapeutic mild donor hypothermia. In The Lancet Respiratory Medicine, the HYPOREME Trial Group reports the results of the multicentre, randomised controlled HYPOREME trial, which assessed the hypothesis that mild donor hypothermia (34–35°C) could decrease the frequency of delayed graft function in recipients of kidneys from expanded criteria donors in whom death was diagnosed based on neurological criteria, compared with normothermia (36·5–37·5°C). The trial was conducted at 53 intensive care units and transplant centres in France between 2017 and 2022, and enrolled 365 expanded criteria donors, 298 of whom provided kidneys to 526 recipients; 470 recipients (89%) received kidneys stored using hypothermic machine perfusion. In HYPOREME, delayed graft function occurred in 40 (16%) of 251 recipients in the hypothermia group versus 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]). Post-hoc sensitivity analyses were consistent with this finding. Although most secondary outcomes did not differ between the two groups, at 1 year after transplantation, recipients in the hypothermia group had better kidney function (lower mean serum creatinine concentrations and higher estimated glomerular filtration rate) than recipients in the normothermia group. HYPOREME is a landmark study that addresses an important clinical question in the field of transplantation medicine, for which evidence is sparse and guidelines are lacking. The trial adds novel data to the literature and provides meaningful insights for several stakeholders.