Altered Expression of Inflammation Genes in Preimplantation Kidney Biopsies of Extended Criteria Donors

Abstract

Background Changes to an organ can occur at the time of brain death and a series of inflammatory proteins are generated within the organ. It is not known whether this inflammatory similarly affects the kidneys from extended (ECD) and standard (SCD) criteria donors and because we have previously reported that preimplantation kidney biopsies from ECD donors have a heavier inflammatory profile when compared with SCD donors. In the present study we extended our results using great number of genes and seeking to identify some immunologic pathways involved in the mechanism of sterile inflammation. Methods Pretransplant kidney biopsies (Bx) were obtained from ECD (n=40) and SCD (n=40). Gene expression profile measured by Real Time qPCR Array representing expression levels of genes indicative of inflammation (IL-10, IL-1b, TNF-α, MCP-1, NFK-b, TLR-4, HMGB1, IFN-gamma, TGF-b, Myd-88), cytoprotection (HO-1, HIF-1a), apoptose (CASP-1) and intercellular adhesion (ICAM-1) and correlated with donor variables. Results ECD donors were older had more cerebrovascular accident, arterial hypertension and diabetes (p<0.01) and recipients of ECD kidneys had renal function and 24h proteinuria worst 1 year after transplantation (p<0.006). Genes IL-10, IL-1 β, TLR-4, HMGB-1, HIF-1 and CASP-1 were significantly more expressed in biopsies from ECD than SCD. Presence of DGF, acute rejection, was not associated with any individual transcript. Conclusions The present results confirm and expand our previous findings that ECD kidney is highly inflamed when compared with SCD and that a Myd-88 independent pathway of innate immunity may be activated. We appreciate the FAPESP (#2014/25831-5) for the financial support.