Association of Sex with Risk of Kidney Graft Failure Differs by Age

Abstract

Prior studies of sex differences in kidney graft survival showed conflicting results. We hypothesized that the association between recipient sex and kidney graft failure risk differs by recipient age and donor sex. We evaluated 159,417 patients recorded in the Scientific Registry of Transplant Recipients database who received a first deceased-donor kidney transplant (1995-2013). We used time-varying Cox models to estimate the association between recipient sex and death-censored graft failure. Models, stratified on donor sex and adjusted for potential confounders, included a recipient sex by current age interaction term. Among recipients of male donors, females of all ages had significantly higher graft failure risks than males (adjusted hazard ratios 0-14 years: 1.51 [95% confidence intervals 1.19 to 1.90]; 15-24 years: 1.37 [1.18 to 1.59]; 25-44 years: 1.14 [1.03 to 1.26]; 45 years: 1.05 [1.01 to 1.09]). Among recipients of female-donor grafts, only female recipients aged 15-24 years had a significantly higher graft failure risk than their male counterparts had (1.28 [1.06 to 1.53]). Indeed, female recipients aged ≥45 years had a significantly lower graft failure risk than their male counterparts had (0.95 [0.91 to 0.99]). These observations might be explained by the combined influence of several factors, including recognition of sex-determined minor histocompatibility antigens, influence of sex hormones on immune activation, sex- and age-related differences in medication adherence, and sex-related differences in body size. Additional studies should determine whether sex- and age-specific immunosuppression strategies are warranted for kidney graft recipients.

Keywords: Epidemiology and outcomes; kidney transplantation; transplant outcomes.

Figure 1.

Crude death-censored graft failure rates are higher in young female than young male recipients. When the donor is male (A), sex differences are prominent among recipients <25 years old. When the donor is female (B), failure rates are slightly higher in females than males <25 years and slightly lower in females than males ≥45 years. Because age was treated as a time-varying variable, individuals could contribute person-time to multiple current-age intervals. Rates are provided in tabular form in the Supplemental Material. p-years, person years.

Figure 2.

Relative hazards of death censored graft failure in female versus male recipients differ by age and by donor sex. Adjusted hazards of death-censored graft failure are significantly higher in females relative to males of all ages when the donor is male (A). When the donor is female (B) females 15–24 years have significantly higher graft failure risks than males the same age, whereas risks are lower in females than males ≥45 years. Hazard ratios are shown with 95% CIs. Final models were adjusted for race, primary cause of ESRD, duration of dialysis pretransplant, donor age, donor weight, recipient weight, and panel reactive antibody. HR, hazard ratio.