Association of Complement C3 Gene Variants with Renal Transplant Outcome of Deceased Cardiac Dead Donor Kidneys

Abstract

Local renal complement activation by the donor kidney plays an important role in the pathogenesis of renal injury inherent to kidney transplantation. Contradictory results were reported about the protective effects of the donor C3F allotype on renal allograft outcome. We investigated the influence of the donor C3F allotype on renal transplant outcome, taking all different donor types into account. C3 allotypes of 1265 donor-recipient pairs were determined and divided into four genotypic groups according to the C3F allotype of the donor and the recipient. The four genotypic groups were analyzed for association with primary nonfunction (PNF), delayed graft function, acute rejection, death-censored graft survival and patient survival. Considering all donor types, multivariable analysis found no association of the donor C3F allotype with renal allograft outcome. Also, for living and deceased brain-dead donors, no association with allograft outcome was found. Post hoc subgroup analysis within deceased cardiac dead (DCD) donors revealed an independent protective association of donor C3F allotype with PNF. This study shows that the donor C3F allotype is not associated with renal allograft outcome after kidney transplantation. Subgroup analysis within DCD donors revealed an independent protective association of the donor C3F allotype with PNF, which is preliminary and warrants further validation.

Donor and recipient genetic variants in NLRP3 associate with early acute rejection following kidney transplantation

“…Samples were collected from a retrospective cohort as described before3536. Between March 1993 and February 2008, 1271 matching donor and recipient peripheral blood mononuclear cells (PBMCs) were obtained from all available patients who underwent kidney transplantation at the University Medical Center Groningen, The Netherlands.…”

Proteomic profiling of heterotopic heart-transplanted rats using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry: Potential biomarkers and drug targets

“…12,13 Another study failed to confirm an association between C3 polymorphisms and transplant outcome.…”

Complement—here, there and everywhere, but what about the transplanted organ?

“…Poor graft function has also been associated with tubuloepithelial complement deposition on pre-implantation biopsies [138]. C4d deposition identified on transplant biopsies has been synonymous with AMR [139].…”

“…Donor C3 has previously been described to be associated with the risk of graft dysfunction [138]. A microarray analysis of complement in donors prior to transplantation showed high levels of C3 in organs with a poor allograft function at 3 years follow up [19].…”

“…C4d deposition identified on transplant biopsies has been synonymous with AMR [139]. In addition, serological tests have been developed to determine complement fixing HLA-specific antibodies that have been reported to have a higher sensitivity to underlying episodes rejection [138]. Detection of serum anti-HLA antibodies binding C1q in kidney transplantation have also been associated with poor graft function [89].…”