*Purpose: Despite improvements in organ preservation techniques and efforts to minimize the duration of cold ischemia, ischaemia- reperfusion injury remains associated with poor graft function and decreased long-term survival in kidney transplantation. We recently demonstrated a clinically significant daytime variation in myocardial tolerance to the controlled ischaemia-reperfusion insult imposed during cardiac surgery. Indeed, patients undergoing aortic valve replacement in the afternoon display lower perioperative myocardial injury and postoperative morbidity than those operated on in the morning. Interestingly, this daytime variation of perioperative myocardial injury was transcriptionally orchestrated by the myocardial circadian clock. In line with our previous demonstration in cardiac surgery, we hypothesized that kidney graft tolerance to the mandatory ischemia-reperfusion would depend on the time-of-day of clamping/declamping, which would impact graft and patient survival.

*Methods: We studied 1-year (and 3-years) patient and graft post-transplant survival in cohorts of 10292 (7606) patients firstly transplanted in France between 2006 and 2017 (2015), from 8413 (and 6219) brain-dead donors. The impact of time-of-day of clamping and declamping, corresponding respectively to the start of kidney ischemia and to reperfusion, as well as ischemia duration was specifically investigated.

*Results: As expected, a prolonged ischemia time decreased significantly post-transplant mid-term survival. Although time-of-day of clamping was not associated with outcomes, a daytime (vs night-time) declamping time significantly increased post-transplant early survival. The association between daytime declamping and improved outcomes (patient and graft post-transplant survival) remained significant after adjustment for other predictors (HR= 1.29 [1.11-1.49] for nighttime vs daytime declamping, p=0.0006 by Cox multivariable analysis). Interestingly, the deleterious impact of prolonged ischemia duration (>15 hours) was significantly compensated by a daytime (vs nighttime) declamping ; although the best results were achieved with daytime declamping and ischemia duration <15h.

*Conclusions: Daytime declamping significantly improves the prognosis of kidney transplantation. Our results could impact the planning of kidney transplantation surgery simultaneously to ischemia duration in order to enhance graft survival and consequently decrease the cost related to graft failure.

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