Rapid or slow time to brain death? Impact on kidney graft injuries in an allotransplantation porcine model

Thomas Kerforne (1, 2) , Sébastien Giraud (1, 2, 3) , Jerome Danion (2) , Raphael Thuillier (1, 2, 3) , Pierre Couturier (4, 2, 1) , William Hebrard (5, 4) , Olivier Mimoz (2, 3, 6) , Thierry Hauet (1, 2, 3, 4)

1 IRTOMIT [Poitiers] - Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques [U 1082]
2 CHU de Poitiers [La Milétrie] - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
3 Université de Poitiers - Faculté de Médecine et de Pharmacie
4 IBiSA Plateforme, Plate-forme MOdélisation Préclinique - Innovation Chirurgicale et Technologique (MOPICT)
5 GenESI - Génétique, Expérimentation et Système Innovants
6 PHAR [Poitiers] - Pharmacologie des anti-infectieux

The use of donors deceased after brain death (DBD) with extended criteria in response to the shortage of grafts leads to the removal of more fragile kidneys. These grafts are at greater risk of not being grafted or delayed function. A better knowledge of the pathophysiology of DBDs would improve this situation. There is a difference between the results from animal models of DBD and the clinical data potentially explained by the kinetics of brain death induction. We compared the effect of the induction rate of brain death on the recovery of post-transplant renal function in a pig model of DBD followed by allografts in nephrectomized pigs. Resumption of early function post-transplant was better in the rapidly generated brain death group (RgBD) and graft fibrosis at three months less important. Two groups had identical oxidative stress intensity but a greater response to this oxidative stress by SIRT1, PGC1-α and NRF2 in the RgBD group. Modulation of mechanistic target of rapamycin (mTOR) stimulation by NRF2 would also regulate the survival/apoptosis balance of renal cells. For the first time we have shown that an allostatic response to oxidative stress can explain the impact of the rapidity of brain death induction on the quality of kidney transplants.

Mots clés: mechanistic target of rapamycin; brain death; kidney; transplantation; oxidative stress; allostasis; nuclear factor erythroid-2-related factor 2

Domaines: Médecine humaine et pathologie

Thomas Kerforne, Sébastien Giraud, Jerome Danion, Raphael Thuillier, Pierre Couturier, et al.. Rapid or slow time to brain death? Impact on kidney graft injuries in an allotransplantation porcine model. International Journal of Molecular Sciences, 2019, 20 (15), pp.3671. ⟨10.3390/ijms20153671⟩. ⟨hal-02270575⟩