title: Role of warm ischemia on innate and adaptive responses in a preclinical renal auto-transplanted porcine model.
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.
authors.forename: Ludivine
authors.initials: L
authors.lastname: Rossard
authors.forename: Frédéric
authors.initials: F
authors.lastname: Favreau
authors.forename: Sebastien
authors.initials: S
authors.lastname: Giraud
authors.forename: Raphael
authors.initials: R
authors.lastname: Thuillier
authors.forename: Sylvain
authors.initials: S
authors.lastname: Le Pape
authors.forename: Jean Michel
authors.initials: JM
authors.lastname: Goujon
authors.forename: Alexandre
authors.initials: A
authors.lastname: Valagier
authors.forename: Thierry
authors.initials: T
authors.lastname: Hauet
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D016923:Cell Death; D003080:Cold Temperature; D005355:Fibrosis; D007113:Immunity, Innate / Q000276:immunology*; D007249:Inflammation / Q000473:pathology; D007677:Kidney Function Tests; D016030:Kidney Transplantation; D007684:Kidney Tubules / Q000473:pathology; D008297:Male; D023421:Models, Animal; D010084:Oxidation-Reduction; D015427:Reperfusion Injury / Q000276:immunology / Q000652:urine; D034421:Sus scrofa; D013997:Time Factors; D014182:Transplantation, Autologous; D052096:Warm Ischemia