Abstract
BackgroundDeceased 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.MethodsUsing 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.ResultsWI + 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.ConclusionsThe 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.
Highlights
Deceased after cardiac arrest donor are an additional source of kidney graft to overcome graft shortage
Donor deceased after cardiac death (DCD), is an additional potential source of kidney graft which is more prone to severe ischemia reperfusion injury (IRI), primary non-function (PNF), and delayed graft function
A significant increase in creatininemia was observed in experimental groups subjected to ischemia from H3 maintained at D3, with the highest level attained in warm ischemia (WI) + cold ischemia (CS) (Table 1)
Summary
Deceased after cardiac arrest donor are an additional source of kidney graft to overcome graft shortage. Donor deceased after cardiac death (DCD), is an additional potential source of kidney graft which is more prone to severe ischemia reperfusion injury (IRI), primary non-function (PNF), and delayed graft function (DGF). In such donors, different ischemic conditions are associated such as warm ischemia (WI) and cold ischemia (CS) characterized respectively by an ischemic period at body temperature initiated by cardiac arrest ensuing a low and/or no blood flow and by a hypothermic preservation of kidneys. There is a strong body of evidence that the consequences of IRI are identifiable in an increased acute rejection rate [5,6]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call