Contributors: Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U 1011 (RNMCD); Institut Pasteur de Lille; Pasteur Network (Réseau International des Instituts Pasteur)-Pasteur Network (Réseau International des Instituts Pasteur)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille); Agence de la biomédecine Saint-Denis la Plaine; Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille); Centre de recherche en épidémiologie et santé des populations (CESP); Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay; No funding was required for this study which falls within the missions of the agence de la biomédecine. BS and DM are supported by grants from Agence Nationale pour la Recherche (ANR-16-RHUS-0006-PreciNASH, ANR-10-LABX-0046, ANR TOMIS-Leukocyte: ANR-CE14-0003-01 and ANR CALMOS: ANR-18-CE17-0003-02), the Leducq Foundation LEAN Network 16CVD01 and the National Center for Precision Diabetic Medicine–PreciDIAB (ANR-18-IBHU-0001; 20001891/NP0025517; 2019_ESR_11). BS is a recipient of an Advanced ERC Grant (694717).; ANR-16-RHUS-0006,PreciNASH,PreciNASH(2016); ANR-10-LABX-0046,EGID,EGID Diabetes Pole(2010); ANR-19-CE14-0003,TOMIS-leukocyte,Impact du moment de la journée sur la réaction inflammatoire péri-opératoire et le remodelage cardiaque inverse après remplacement valvulaire aortique(2019); ANR-18-CE17-0003,CALMOS,Homéostasie calcique mitochondriale dans le contrôle des troubles du rythme associés à la cardiomyopathie métabolique(2018); ANR-18-IBHU-0001,PreciDIAB,PreciDIAB Institute, the holistic approach of personal diabets care(2018); European Project: 694717,H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) ,ImmunoBile(2016)
Abstract: International audience ; Despite improvements in organ preservation techniques and efforts to minimize the duration of cold ischemia, ischemia–reperfusion (IR) injury remains associated with poor graft function and long-term survival in kidney transplantation. We recently demonstrated a clinically significant day-time variation in myocardial tolerance to IR, transcriptionally orchestrated by the circadian clock. Patient and graft post-transplant survival were studied in a cohort of 10,291 patients first transplanted between 2006 and 2017 to test whether kidney graft tolerance to IR depends on the time-of-the-day of clamping/declamping, and thus impacts graft and patient survival. Post-transplant 1- and 3-year survival decreased with increasing ischemia duration. Time-of-the-day of clamping did not influence outcomes. However, night-time (vs. day-time) declamping was associated with a significantly worse post-transplant survival. After adjustment for other predictors, night-time (vs. day-time) declamping remained associated with a worse 1-year (HR = 1.26 (1.08–1.47), p = 0.0028 by Cox multivariable analysis) and 3-year (HR = 1.14 (1.02–1.27), p = 0.021) outcome. Interestingly, the deleterious impact of prolonged ischemia time (>15 h) was partially compensated by day-time (vs. night-time) declamping. Compared to night-time declamping, day-time declamping was associated with a better prognosis of kidney transplantation despite a longer duration of cold ischemia.
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