Pregnancy-Induced Sensitization Promotes Sex Disparity in Living Donor Kidney Transplantation

Abstract

The presence of sex disparity in living donor kidney transplantation (LDKT) remains controversial. To determine if women fall behind men in LDKT evaluation, we performed an intention to treat study of 2587 candidates listed for kidney transplant at a single transplant center over 7 years. We found that women and men kidney transplant candidates engaged an equivalent type and number of prospective living donors. However, sex-specific differences in sensitization history and histocompatibility reduced the rate of LDKT for women by 30%. Pregnancy-induced incompatibility with spouse donors was limiting given that spouses were among the individuals most likely to complete donation. Notably, participation in a kidney paired exchange program eliminated sex-based differences in LDKT. Collectively, these data suggest that pregnancy is a formidable biologic barrier for women and contributes uniquely to sex disparity in LDKT. Targeted efforts to improve transplant center participation in paired kidney exchanges may increase sex equity in LDKT.

Keywords: disparity; gender difference; kidney donation; kidney transplantation; pregnancy.

Figure 1.

Sex differences in LDKT evaluation arise during histocompatibility testing. (A) Frequency of LD referral, crossmatch (XM), and transplantation for all patients listed for kidney transplantation (men=1593; women=994). The table indicates the number of listed patients in each group. *P=0.01. (B) Average number of LD referrals per candidate (among candidates with at least one LD referred; n=807). Error bars represent SD. *P=0.03. (C) Distribution of relationship of referred LDs. The table indicates percentage of donors in each group. It excludes donors with an undocumented relationship to the candidate (n=12 referred donors [men]; n=20 referred donors [women]). M, men; W, women. *P<0.01 (spouses, men versus women). (D) Rate of LDKT among candidates with complete data who were XM with an LD (n=502; men =293, women =209). *P<0.01. (E) Wait times for patients who were transplanted by sex (men =171, women =118). Error bars represent SD. *P=0.02.

Figure 2.

The greater burden of sensitization in female LDKT candidates is underestimated by cPRA. (A) Frequency of living donor incompatibility in women versus men LDKT candidates. *P<0.001. (B) Frequency and magnitude of sensitization between men and women LDKT candidates. The bar graph represents the percentage of men or women with each sensitizing event. The table indicates the number of candidates in each group. X indicates mean cPRA for men and women in each group. Preg, pregnancy; Tfn, transfusion; Txp, prior transplant; Uns, unsensitized. (C) Frequency of living donor incompatibility as a function of cPRA. The dotted line represents a 1:1 correlation between living donor incompatibility and cPRA. *P=0.02.

Figure 3.

Pregnancy promotes living donor incompatibility to a greater degree than prior transplantation or blood transfusion. (A) Frequency of living donor incompatibility as a function of cPRA for candidates with a history of a sensitizing event. The dotted line represents a 1:1 correlation between living donor incompatibility and cPRA. Transfusion and transplantation groups include both men and women. Number of crossmatched donors is shown in the table for each group. *P<0.001; **P=0.04; ***P=0.01. (B) Frequency of incompatible donor type among candidates grouped by sensitizing event. Number of crossmatched donors is shown in the table for each group. Candidates sensitized by prior transplant or transfusion include men and women, except when crossmatched with an offspring living donor (men only). XM, crossmatched. *P<0.001; **P=0.02.

Figure 4.

Utilization of compatible living donors reveals the impact of pregnancy-induced incompatibility on women. (A) Living donor utilization among compatible donor types. Men are shown in black, and women are shown in gray. The number of compatible prospective donors per group is shown. Ext Fam, extended family; Unrel, unrelated. *P=0.05. (B) Effect of sensitizing event on utilization of offspring or spouse living donors (upper panel) and extended family or unrelated living donors (lower panel). Number of compatible prospective donors per group is shown. Not applicable (N/A; women) indicates that, by definition, offspring were not available for crossmatch among women sensitized only by transfusion or transplantation. No spouses were used among women sensitized by transfusion or transplantation alone. Preg, pregnancy; Tfn, transfusion; Txp, prior transplant; Uns, unsensitized. *P=0.02.