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Fri, March 28th, 2014, 10:00 - 10:10

Functional EPO gene polymorphism rs1617640 affects graft survival after deceased donor kidney transplantation

W.G. van Rijt, J. Damman, H. Snieder, M.A. Seelen, H. van Goor, G. Navis, J. van den Born, M.H. de Borst, B.G. Hepkema, J.L. Hillebrands, R.J. Ploeg, S.J.L. Bakker, H.G.D. Leuvenink

Moderator(s): S.A. Nurmohamed en M. Seelen

Location(s): Grote zaal

Category:

Introduction High erythropoietin (EPO) levels following renal transplantation have been associated with increased mortality. However, EPO also has an alleged cytoprotective function. In this study we investigated the role of the functional promotor single nucleotide polymorphism, rs1617640, in deceased donor kidney transplantation. Materials & Methods In 986 deceased donors and 981 recipients of a deceased donor kidney the genotype of rs1617640 was determined. Subsequently, the effect of the different genotypes on death censored graft survival, primary non-function, delayed graft function and acute rejection was studied in recipients and donors. Cox regression analyses or binary logistic regression were performed adjusting for all factors potentially influencing outcome parameters: donor age, donor sex, donor type, recipient age, recipient sex, total mismatch, cold ischemia time, sequence number of transplantation. Furthermore, plasma EPO levels were measured in a part of the cohort. Results The TT genotype of EPO SNP rs1617640 in deceased donor kidneys was associated with reduced death censored graft survival (84% vs. 92%; p=0.045) and an increased incidence of delayed graft function (39% vs. 29%; p=0.012) compared to the GG genotype. Plasma EPO levels were significantly higher in TT genotype recipients compared to GG genotype, while high plasma EPO levels were not associated with reduced graft survival. Plasma EPO levels seemed to be related to the genotype of the recipient and not the genotype of the donor. Discussion This is the first study showing the association between functional promotor EPO single nucleotide gene polymorphism rs1617640 and graft survival following deceased donor kidney transplantation. The TT genotype in deceased donor kidneys impaired short- and long-term outcome independent of plasma EPO levels. The GG genotype seems more sensitive for EPO and presumably the cytoprotective pathways of EPO are thereby more efficiently activated. These findings give new insights in the role of EPO in renal transplantation and may help translate EPO mediated cytoprotection to the transplantation clinic.