134-P

Abstract

Aim Delayed graft function (DGF) remains a major problem in solid organ transplantation, as it adversely impacts both short and long term outcomes. There is evidence that activation of the innate immune system triggered by “danger signals” associated with brain death and/or ischemia-reperfusion injury (IRI) plays a significant role in the pathogenesis of DGF. The objective of this work was to investigate association between expression of the innate immunity genes TLR4, TLR2, MYD88, TRIF, SARM1, NOD1 and NOD2 in deceased donor (DD) grafts and occurrence of DGF. Methods Expression levels were evaluated in pre-implantation biopsies (PIB) from kidneys of 72 DD and 18 living donors (LD). DGF was defined as dialysis requirement within the first week after transplantation (Tx). Total RNA was extracted from PIB with RNeasy Mini Kit (Qiagen). Relative expression (2-ΔΔCt method) of the innate immunity genes and TATA-binding protein (TBP, used as internal control) were obtained by Taqman assays (Applied Biosystems). Statistics: Mann-Whitney and Fisher’s exact tests; significance was set at p Results SARM1 and TRIF expression did not differ between DD and LD, neither between cases with and without DGF. Expression levels of TLR4, TLR2, MYD88, NOD1 and NOD2 were higher in DD than in LD kidneys, but only NOD1 expression was higher in DD transplants with than without DGF (1.7 vs 1.4, p = 0.03). Conclusions Overall, these data emphasize the involvement of innate immunity in the physiopathology of kidneys from DD; the fact that TRIF was not differentially expressed in DD kidneys suggests that TLR4 signaling in this setting occurs preferentially through MyD88-dependent pathway; among all genes tested, only the expression of NOD1 showed association with the occurrence of DGF.