1. Role of warm ischemia on innate and adaptive responses in a preclinical renal auto-transplanted porcine model
- Author
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Thierry Hauet, Jean Michel Goujon, Sébastien Giraud, Frédéric Favreau, Alexandre Valagier, Ludivine Rossard, Sylvain Le Pape, Raphael Thuillier, Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Biochimie [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers, Groupement Scientifique - Ibisa (Ibisa), Institut National de la Recherche Agronomique (INRA), This work was supported by grants from the Ministère Français de l'Enseignement Supérieur et de la Recherche, Conseil Régional Poitou-Charentes, University of Poitiers, Banque Tarneaud, University Hospital of Poitiers, Institut National de Recherche Agronomique and French Society of Organ Transplantation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Poitiers, Groupement Scientifique - Ibisa (IBISA), and BMC, Ed.
- Subjects
Male ,Innate immune response ,Pathology ,Time Factors ,[SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery ,Sus scrofa ,030232 urology & nephrology ,Adaptive Immunity ,030230 surgery ,Kidney Function Tests ,Kidney transplantation ,Preclinical porcine model ,0302 clinical medicine ,Fibrosis ,Warm Ischemia ,Medicine(all) ,Kidney ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,Cell Death ,Ischemia-reperfusion ,Adaptive immune response ,ISCHEMIA/REPERFUSION INJURY ,REPERFUSION INJURY ,COLD ISCHEMIA ,IMMUNE-RESPONSE ,GRAFT FIBROSIS ,KIDNEY ,INFLAMMATION ,ALLOGRAFTS ,APOPTOSIS ,PRESERVATION ,General Medicine ,Cold Temperature ,Kidney Tubules ,medicine.anatomical_structure ,Reperfusion Injury ,Models, Animal ,medicine.symptom ,Oxidation-Reduction ,medicine.medical_specialty ,Ischemia ,Cold storage ,Inflammation ,[SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery ,Transplantation, Autologous ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,medicine ,Animals ,Biochemistry, Genetics and Molecular Biology(all) ,business.industry ,Research ,medicine.disease ,Immunity, Innate ,Transplantation ,business ,Reperfusion injury ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
Background Deceased after cardiac arrest donor are an additional source of kidney graft to overcome graft shortage. Deciphering the respective role of renal warm and cold ischemia is of pivotal interest in the transplantation process. Methods Using a preclinical pig model of renal auto-transplantation, we investigated the consequences of warm and cold ischemia on early innate and adaptive responses as well as graft outcome. Kidneys were subjected to either 60 min-warm ischemia (WI) or auto-transplanted after cold storage for 24 h at 4°C (CS), or both conditions combined (WI + CS). Renal function, immune response and cytokine expression, oxidative stress and cell death were investigated at 3 h, 3 and 7 days (H3, D3 and D7) after reperfusion. At 3 months, we focused on cell infiltration and tissue remodelling. Results WI + CS induced a delayed graft function linked to higher tubular damage. Innate response occurred at D3 associated to a pro-oxidative milieu with a level dependent on the severity of ischemic injury whereas adaptive immune response occurred only at D7 mainly due to CS injuries and aggravated by WI. Graft cellular death was an early event detected at H3 and seems to be one of the first ischemia reperfusion injuries. These early injuries affect graft outcome on renal function, cells infiltration and fibrosis development. Conclusions The results indicate that the severe ischemic insult found in kidneys from deceased after cardiac arrest donor affects kidney outcome and promotes an uncontrolled deleterious innate and adaptive response not inhibited 3 months after reperfusion.
- Published
- 2013