H-Y Effect Increases Early Kidney Graft Failure
Reported July 30, 2009
HOUSTON, July 30 — Women who receive kidneys from deceased male donors have an increased risk of graft failure during the first year but not after that, a review of a large transplant database showed.
Female recipients of kidneys from deceased male donors had a statistically significant 12% higher rate of graft failure at one year, according to S. Joseph Kim, MD, of the University of Toronto, and John S. Gill, MD, of the University of British Columbia.
By 10 years, the graft failure rate was similar for male-female transplantations and all other sex combinations, the researchers reported online in the Journal of the American Society of Nephrology.
“We observed a similar pattern of short- and long-term risk for both death-censored graft failure and mortality,” the authors reported. “The main results were consistent across several prespecified patient subgroups and were robust to sensitivity analyses.”
Studies of organ transplantation have yielded mixed results regarding outcomes in female recipients of male donor organs.
One recent European study of a large transplant database showed that female recipients of male, deceased-donor kidneys had a 6% to 8% greater risk of graft failure and a 10% to 11% greater risk of death-censored graft failure at 10 years compared with all other sex combinations (Lancet 2008; 372: 49-53).
Authors of that report termed the phenomenon the “H-Y effect,” referring to reactivity against H-Y encoded gene products.
But a similar study of a U.S. transplant database showed no such effect, Drs. Kim and Gill said. In addition, the more recent study did not adjust for an extensive set of covariates.
In an attempt to validate the European findings, Drs. Kim and Gill performed a retrospective cohort study, using data from the U.S. Renal Data System.
They used a modeling strategy similar to the one used in the European study but included additional covariates, evaluated prespecified subgroups, and performed various sensitivity analyses.
The cohort had a median follow-up of 4.16 years for graft failure and 5.45 years for mortality, resulting in 548,904 and 660,602 person-years at risk for graft failure and patient mortality, respectively.
During the first year of follow-up, 16,135 graft failures occurred. An additional 35,084 graft failures occurred from the second through 10th years, including 22,566 deaths.
Compared with all other donor-recipient sex combinations, female recipients of male deceased-donor kidneys had a one-year graft failure hazard ratio of 1.12 (95% CI 1.05 to 1.19). At 10 years, the hazard ratio had declined to 1.03 and was no longer statistically significant (95% CI 0.98 to 1.07).
The findings remained essentially unchanged in subgroup analyses that included recipient and donor race, cause of end-stage renal disease, HLA mismatched, peak panel-reactive antibody, and year of transplantation.
They noted that the study may have been limited by lack of complete information on confounders and that “residual confounding is always a concern in the setting of observational studies of registry data.”
Primary source: Journal of the American Society of Nephrology
Source reference:
Kim SJ, Gill JS “H-Y incompatibility predicts short-term outcomes for kidney transplant recipients” J Am Soc Nephrol 2009; DOI: 10.1681/ASN.2008101110.