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.

Biologic mechanisms and clinical consequences of pregnancy alloimmunization

“…Nevertheless, these efforts illustrate that the magnitude and spectrum of pregnancy alloimmunization are likely to be vastly underestimated when alloantibody alone is used to identify alloimmunized individuals. 12 As these effects are obviously not observed in men, this study identified pregnancy alloimmunization as a major contributor to sex disparity in living donor kidney transplantation. These studies have focused on kidney transplant candidates given the well- Despite these data, the true cost of pregnancy alloimmunization on kidney transplant access remains difficult to project as few studies have examined how many women have lost access to transplantation because of pregnancy-induced incompatibility with a potential donor.…”

“…10 Although this important study reveals the scale of the immunomodulation that occurs during pregnancy, it remains unknown which of these changes is driven specifically by exposure to fetal alloantigen (ie, alloimmunization) or whether these changes occur because of other antigen nonspecific mechanisms. 12 Whether this is due to low-level antibody or differences in HLA allele frequency within a candidate's living donor pool remains unclear. More-detailed analyses of the UNOS registry 11 as well as singlecenter reports 12 illustrate the degree to which pregnancy contributes to this increased burden of sensitization among women.…”

“…More-detailed analyses of the UNOS registry 11 as well as singlecenter reports 12 illustrate the degree to which pregnancy contributes to this increased burden of sensitization among women. 12 Hence, the impact of pregnancy alloimmunization is not solely limited to increased wait times and diminished transplant frequency in women. While cPRA estimates donor access to some degree, a recent study highlights the extent to which cPRA underestimates incompatibility in women crossmatched with a living donor.…”

Inferior long-term allograft and patient outcomes among recipients of offspring living donor kidneys

“…Adult offspring remain a prevalent source of potential living donors for kidney transplant candidates (1,9). Although the utilization of offspring living donors has diminished in recent years in the United States (see Supplemental Figure 1), these donors may nevertheless represent the optimal choice to maximize long-term benefit in LDKT.…”

“…First-degree genetic relatives (i.e. siblings, parents, offspring) therefore represent a prevalent and accessible pool of well-matched kidneys (1,9) which may optimize long-term allograft outcomes. Among these donor types, offspring ostensibly represent the ideal donor group given the combined benefit of haplotype matching and younger donor age.…”