The significant difference in donor-to-recipient gender pairings between the LRD and LURD groups could have been due to the presence of LURD spousal pairs, which showed a preponderance of female to male donation. An analysis looking only at cross-gender LRD and LURD pairings (male-to-female and female-to-male only) showed that the imbalance favoring female-to-male donation was observed in both the LRD (nonspousal only) and LURD (spousal and nonspousal) groups (63 vs. 71%;P =NS). Conversely, when the spousal pairs were excluded from the overall pairing analysis, there was still a significant difference in gender pairing between LRD and LURD (P =0.001) (Table 5). In this case, there was a strikingly higher proportion of male-to-male transplants (27 vs. 48%) and a lower proportion of male-to-female transplants (18 vs. 9%) in the LURD group.
Previous studies have shown that females are consistently less likely than males to receive transplants from cadaveric or living donors (10–15,17,18,20), and in the case of LD transplantation females are disproportionately more likely to be kidney donors (11,12,19). The reasons are likely multifactorial and include inequalities at multiple levels of the transplantation process from the initiation of renal replacement therapy (RRT) to inclusion on the waiting list and transplantation. These differences have been attributed to clinician-based gender selection bias for initiation of RRT (7,20–22) and referral for waitlisting (13,15), financial differences in access to care (13,16,23), gender-based differences in patient acceptance of aggressive therapy (24,25), medical or immunological contraindications to organ donation or acceptance (12), and a greater attitudinal proclivity to donation among women (19,26,27).
Gender bias appears to exist in the treatment of ESRD itself. The age- and race-adjusted incidence rate for RRT among females is consistently lower than that for males in the United States (28). This difference is even larger in other countries (29,30). Based on a review of death certificates in the United States and Sweden, Kjellstrand and colleagues (20–22) reported that females are more likely to die of uremia without RRT than males in these countries, suggesting that gender bias on the part of clinicians is, in part, responsible for the observed difference. In fact, there is a growing body of literature showing that women receive less aggressive treatment of other diseases as well. For example, several studies have documented gender-based disparities in the use of angiography, cardiac bypass, and cardiac transplantation (14,25,31–35).
The possibility of gender selection bias on the part of physicians and other health care personnel is supported by the findings from a study of 8315 patients receiving dialysis in North Carolina, South Carolina, and Georgia (15). These authors found female gender to be negatively associated with dialysis center staff perceptions of transplant candidacy status even after adjustment for other patient characteristics including illness severity and certain comorbid conditions. Bloembergen et al. (13) reviewed 5 years of data from 1984 to 1989 from the Michigan Kidney Registry and the Organ Procurement Agency of Michigan. They found that after adjusting for a number of factors, women aged 46 to 55 years were 33% less likely to be placed on the cadaveric renal transplant waitlist and women older than 56 years of age were 29% less likely to be waitlisted compared with their male counterparts. This was not the case for women younger than 46 years of age. In a longitudinal cohort study by Garg et al. (36), women were 18% less likely to be activated on the renal transplant waitlist even after adjustment for comorbid medical conditions. Even among children and adolescents with ESRD, female patients were less likely to be listed for transplant than male patients. In a 2-year analysis from 1990 to 1992, McCauley et al. found that employed women and those with a higher education were more likely to be referred to transplantation (14). Homemakers were 83% less likely to be referred for a transplant and 86% less likely to receive one when compared to employed patients in multivariate analyses controlled for age, race, cause of ESRD, comorbidities, and other factors.
The eventual loss of Medicare eligibility after transplantation may serve as a greater deterrent to transplantation for women because of gender differences in income and insurance coverage (13,16). Income may directly influence treatment choices when patients have no coinsurance to meet large expenses not covered by Medicare, such as transportation and outpatient drugs. During much of the time period on which this study focused, Medicare paid 80% of immunosuppressive drugs for only 1 year. A study by Khajehdehi et al. (23) may offer some insight. In this study, females were significantly less likely to be recipients and more likely to be donors of renal allografts, particularly if they were unemployed. All of the living unrelated donors claimed to have altruistic motives for organ donation, but gift rewarding, drug abuse, unemployment, economical deadlock, and urgent need of money were significantly more frequent than among living related donors. Although most US studies either incompletely adjust for income or do not adjust at all, results of a recent Canadian study (18) suggest that financial disincentives are probably not a driving force. In Canada, in which the ability to pay therapy-related costs should not be a factor, men still experienced significantly greater kidney transplantation rates relative to women.
An alternative hypothesis is that women are less likely to desire transplantation because of increased risk aversion or decreased willingness to tolerate the adverse effects of immunosuppression relative to men (24). The idea that women may be more risk averse in medical decisions may be supported by a study of patients with severe heart failure, in which women were found to be more likely than men to refuse cardiac transplantation (25). It has been suggested that women’s roles as caretakers may influence them to refuse cardiovascular surgery (37). However, other evidence in the areas of oncology (38) and kidney transplantation (39) suggest than men and women do not make different treatment decisions. In a survey by Crawford et al. (40), healthy adults in Canada were given a questionnaire using three hypothetical treatment scenarios in which an illness situation was described, a treatment was recommended (thrombolysis for a myocardial infarction, a hip replacement in arthritis, and kidney transplant in ESRD), and the risks and benefits of treatment were described. There were no significant gender differences in hypothetical treatment decisions made by patients nor in the factors affecting those decisions.
The implication is that females with ESRD have less access to transplantation because of physician or institutional gender bias, inadequate financial support, and medical unsuitability; or less utilization of transplantation because of refusal of “dangerous” interventions. The empirical evidence on these issues is limited and needs further investigation.
Donor medical and immunological factors may lead to higher donation rates among women. For example, it has been suggested that a higher incidence of hypertension and coronary artery disease in men may result in a higher rate of male donor exclusion (12). Alternatively, a higher level of preformed antidonor lymphocytotoxic antibodies secondary to exposure to paternal antigens during pregnancy may exclude a higher proportion of women from accepting kidneys from their husbands than vice versa (41). However, studies suggest that discrete medical factors, such as medical or immunological contraindications to donation, do not contribute to the gender disparity. In a study by Zimmerman et al. (19), nearly equal proportions of male and female potential donors were excluded because of medical illness or ABO incompatibility.
Alternatively, psychosocial or cultural factors may influence women toward donation. In 1972, Simmons and Fulton (27) compared individuals who had signed an organ donor card to neighbors who had not signed a card. They identified young women as one of the major demographic groups willing to be considered as a cadaveric donor. Simmons et al. (26) found that, compared to men, women were more likely to perceive donation as an extension of their obligation to the family. Men were more likely to be ambivalent about donating a kidney. In addition, men who donated were more likely to believe they had done something heroic compared with women. In another study, the predominance of women among spousal donors was not found to be the result of greater aggressiveness among husbands in soliciting donations from their wives, but rather wives volunteering to donate a kidney because of the impact of the husband’s illness on family life (19).
In our study the significantly older age of recipients and donors in the unrelated group was probably reflective of several factors: the absence of sibling and child recipients in this group, the large number of spousal pairings which are inherently of adult age, and the fact that adolescent friends of pediatric recipients cannot donate.
The results of our study show that even after the exclusion of gender-imbalanced spousal donations, females are significantly less likely to be recipients and more likely to be donors of renal allografts in living renal transplants. These results are similar to reports from other centers and registries, which place women as predominant donors. Although women may have cultural or attitudinal proclivities toward donation, it is the responsibility of the healthcare system to ensure that women experience neither active nor unintentional discrimination. Epidemiological or prospective clinical studies that include data on insurance, income, matching, comorbidities, preformed lymphocytotoxic antibody status, patient preferences, health attitudes, and beliefs are necessary to further delineate the precise factors that contribute to the apparent barriers to transplantation for females. The data set used in these analyses did not include these variables. In the meantime, increased awareness of these gender differences may lead to improvements in modifiable factors including continued efforts to consider transplantation and increase waitlisting for women with ESRD, and closer evaluation of economic influences on donation.
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