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Open Access Research

Role of warm ischemia on innate and adaptive responses in a preclinical renal auto-transplanted porcine model

Ludivine Rossard1, Frédéric Favreau123, Sebastien Giraud13, Raphael Thuillier13, Sylvain Le Pape12, Jean Michel Goujon123, Alexandre Valagier1 and Thierry Hauet1234*

Author Affiliations

1 Inserm U1082, Poitiers, F 86000, France

2 Université de Poitiers, Faculté de Médecine et de Pharmacie, Poitiers, F 86000, France

3 CHU de Poitiers, Service de Biochimie, Poitiers, F 86000, France

4 INRA, IBISA, Domaine expérimental du Magneraud, Surgères F 17700, France

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Journal of Translational Medicine 2013, 11:129  doi:10.1186/1479-5876-11-129

Published: 24 May 2013

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.

Keywords:
Ischemia-reperfusion; Adaptive immune response; Innate immune response; Kidney transplantation; Preclinical porcine model