Donor-recipient sex mismatch in kidney transplantation

Gend Med. 2012 Oct;9(5):335-347.e2. doi: 10.1016/j.genm.2012.07.004. Epub 2012 Aug 18.

Abstract

Background: The lack of reliable human proxies for minor (ie, non-HLA) histocompatibility loci hampers the ability to leverage these factors toward improving transplant outcomes. Despite conflicting reports of the effect of donor-recipient sex mismatch on renal allografts, the association between acute rejection of renal allografts and the development of human alloantibodies to the male H-Y antigen suggested to us that donor-recipient sex mismatch deserved re-evaluation.

Objective: To evaluate whether the relationships between donor sex and allograft failure differed by recipient sex.

Methods: We studied recipients of deceased-donor (n = 125,369) and living-donor (n = 63,139) transplants in the United States Renal Data System. Using Cox proportional hazards models stratified by donor type, we estimated the association between donor-recipient sex mismatch and death-censored allograft failure with adjustment for known risk factors, with and without the use of multiple imputation methods to account for potential bias and/or loss of efficiency due to missing data.

Results: The advantage afforded by male donor kidneys was more pronounced among male than among female recipients (8% vs 2% relative risk reduction; interaction P < 0.01). This difference is of the order of magnitude of several other risk factors affecting donor selection decisions.

Conclusions: Donor-recipient sex mismatch affects renal allograft survival in a direction consistent with immune responses to sexually determined minor histocompatibility antigens. Our study provides a paradigm for clinical detection of markers for minor histocompatibility loci.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Graft Rejection / immunology*
  • Graft Rejection / mortality
  • Graft Survival / immunology*
  • H-Y Antigen / immunology*
  • Histocompatibility / immunology*
  • Humans
  • Kaplan-Meier Estimate
  • Kidney Transplantation / adverse effects*
  • Kidney Transplantation / immunology
  • Kidney Transplantation / mortality
  • Living Donors
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Risk Factors
  • Sex Factors
  • Treatment Outcome
  • United States

Substances

  • H-Y Antigen