Donor-recipient sex mismatch in kidney transplantation.
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.
Department of Medicine, Stanford University School of Medicine, Palo Alto, California, USA. Jane.tan@stanford.edu
Jane C
JC
Tan
Jane P
JP
Kim
Glenn M
GM
Chertow
F Carl
FC
Grumet
Manisha
M
Desai
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000401:mortality; D006085:Graft Survival / Q000276:immunology*; D006182:H-Y Antigen / Q000276:immunology*; D006648:Histocompatibility / Q000276:immunology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology / Q000401:mortality; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012307:Risk Factors; D012737:Sex Factors; D016896:Treatment Outcome; D014481:United States
D006182:H-Y Antigen