Identificação de biomarcadores moleculares em rins de doadores de critério estendido

Abstract

Kidneys from deceased donors with extended criteria (ECD) have been increasingly used, but the outcomes associated with the use of these criteria are still controversial. It is possible that the proinflammatory environment generated by the donor's encephalic death and the activation of innate immunity affect ECD kidneys or with Kidney Donor Profile Index (KDPI) > 80% and the standard donor kidney (SCD) or with KDPI ≤ 80%. Objectives: 1) to investigate the activation of the main innate immunity pathways responsible for the sterile inflammatory response in ECD kidney pre-implantation biopsies and with KDPI > 80%; 2) to compare the gene expression pattern related to innate immunity in pre-implantation biopsies of ECD kidneys and with KDPI > 80%. Methods: Preimplantation kidney biopsies from ECD (n=41) and SCD (n=39) were evaluated for real-time quantitative polymerase chain reaction (qPCR) gene expression using the TaqMan Gene Expression Array Plates system for genes TLR4, HMGB1, NFK-β, MyD-88, INF-γ, IL1-β, TNF-α, CASP1, ICAM-1, IL- 10, HO-1, HIF-1, MCP-1, TGF-β, TRIF, TRAM, IRF-3, RIP1, INFβ-1 and NLRP3. Gene expression was also evaluated in kidneys with KDPI ≥80. Results: ECD biopsies showed a significant increase in expression of IL-10, TLR4, HMGB1, IFN-γ, TRAM, IRF-3, NLRP3, CASP-1, IL-1β and HIF-1 (p < 0.05) compared to the SCD kidneys. Kidneys with KDPI > 80% presented a molecular profile with significant increase of IL- 10, TLR4, HMGB1, TRAM, NLRP3 and IL-1β when compared to KDPI kidneys ≤ 80%. TNF-α and MCP-1 were expressed only in kidneys with KDPI > 80%. Correlation analyzes between gene expression and KDPI scores revealed a significant positive correlation between TLR4, HMGB1, NLRP3, IL-1β, IL-10, TRAM, CASP1, HIF-1, MCP-1, IFN-γ and TNF-α (p < 0.05). Conclusion: Regardless of the classification used to characterize the kidney of the donor we concluded that ECD kidneys and with KDPI > 80% present increased expression of innate immunity genes compared to SCD kidneys or with KDPI ≤ 80%.