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GENDER IMBALANCE IN LIVING DONOR RENAL TRANSPLANTATION1

Kayler, Liise K.; Meier-Kriesche, Herwig-Ulf; Punch, Jeffrey D.; Campbell, Darrell A. Jr,; Leichtman, Alan B.; Magee, John C.; Rudich, Steven M.; Arenas, Juan D.; Merion, Robert M.2

Clinical Transplantation
Free
SDC

Background.  Previous studies have shown more women than men among living donors (LD) and more men among recipients of those kidneys. In this study, we compared the evolving demographics of LD transplants.

Methods.  We retrospectively analyzed all LD transplants performed in our center between 1964 and 2000.

Results.  Among 1182 LD cases, 1035 (88%) were biologically related (LRD) and 147 (12%) were unrelated (LURD). LURD donors and recipients were significantly older than LRD donors and recipients, respectively (P =0.0001). More LURD allograft recipients were male (71%) compared with LRD recipients (57%) (P =0.0013). The proportion of female donors was 55% in both groups. Spousal donations were predominantly wife-to-husband (69%). Compared with the LRD group, there was a greater proportion of female-to-male LURD transplants (46 vs. 30%) and a smaller proportion of female-to-female LURD transplants (10 vs. 25%) (P =0.0001). When spousal pairs were excluded from the analysis, there was a higher proportion of male-to-male (48 vs. 27%) donations and a lower proportion of male-to-female (18 vs. 9%) and female-to-female (25 vs. 17%) transplants in the LURD group (P =0.001).

Conclusions.  Gender disparities in LD transplantation are primarily due to a higher proportion of wife-to-husband donations and a lower incidence of male-to-female grafts among nonspousal LURD transplants. Strategies should be devised to ensure access for women to renal transplantation and to encourage and facilitate donation by men.

Departments of Surgery and Internal Medicine, University of Michigan Health System, Ann Arbor, MI 48109-0331

2 Address correspondence to: Robert M. Merion MD, Department of Surgery, University of Michigan Health System, 2926 Taubman Center, Box 0331, Ann Arbor, MI 48109-0331.

1 Presented at the joint meeting of the American Society of Transplantation and the American Society of Transplant Surgeons, Chicago, IL, May 2001.

Received 27 April 2001.

Revision Requested 29 May 2001.

Accepted 24 June 2001.

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INTRODUCTION

Living donor (LD) transplantation is the preferred treatment modality in most patients with end-stage renal disease (ESRD), because of advantages in survival, quality of life, and cost-effectiveness when compared to maintenance hemodialysis and also cadaveric transplantation (1–6). Living related donor (LRD) renal transplantation is associated with the highest patient and graft survival rates (7). Graft survival after living unrelated donor transplantation (LURD) is equivalent to that of haploidentical-related transplantation and superior to that of similarly mismatched cadaveric grafts (8,9).

Previous studies have shown female gender to be a barrier to access to both living and cadaveric renal transplantation (10–18). In one study of 14,721 patients transplanted between 1981 and 1985, Held et al. (17) found that females were 30% less likely to receive a kidney transplant than males, when adjusted for age, ethnicity, panel reactive antibody level (PRA), income, and dialytic modality. In a national US study of a random sample of 4118 patients with ESRD from 1986 to 1987, Gaylin et al. (10) found that women were 28% less likely to receive a living or cadaveric transplant than men after adjustment for age, ethnicity, PRA, dialytic modality, income, and comorbidity. In a more recent study of 6193 living related transplants based on the United States Renal Data System (USRDS), Bloembergen et al. (12), reported that women were 10% less likely to receive a living-related transplant than men and 28% more likely to donate a kidney than men. Several studies have also documented a predominance of female-to-male donation among spouses in the US (73%) (19) and other countries (86%) (8). However, these studies did not analyze the gender distribution of nonspousal LURD donor-recipient pairings in their cohorts. In this study, we compared demographic characteristics of LRD and LURD transplants to determine the influence of gender pairing and spousal relationship on living kidney donations.

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MATERIALS AND METHODS

The study was a retrospective single center review conducted at the University of Michigan. Electronic medical records of all living related and living unrelated kidney transplants performed between 1964 and 2000 were reviewed. Variables examined were recipient and donor age, gender, ethnicity, date of transplant, etiology of ESRD, and HLA typing. Donor source (living related, living unrelated) and relationship to the recipient were recorded. Statistical analyses included descriptive and comparative statistics based on donor source and relationship, gender, age, and donor-to-recipient gender pairing. Contingency tables were used to compare categorical variables. Two-sided t test was used for continuous variables. P <0.05 was considered statistically significant. All analyses were performed using Statview version 4.5 (Abacus Concepts, Inc., Berkeley, CA).

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RESULTS

A total of 1182 renal transplants from living donors were performed at the University of Michigan Health System between August 1964 and September 2000. The majority of the study population was Caucasian followed by African-American, Hispanic, Middle-Eastern, and other (Table 1). The cause of ESRD was glomerulonephritis in 24%, diabetes in 19%, hypertension in 7%, obstructive uropathy in 5%, polycystic kidney disease in 4%, pyelonephritis in 1%, and other/unknown in 39%. The LD program began in 1964 and the first LURD transplant was done in 1974. A total of 909 LD transplants were first grafts, 228 were second grafts, 49 were third grafts, and 1 was a fourth graft. The relationships of the donors to recipients are shown in Table 2. LURD constituted an increasing proportion of all LD transplants, rising from 1.3% in 1990 to almost 20% in 1999. Among the LD cases, 1035 (88%) were biologically related (LRD) and 147 (12%) were unrelated (LURD). Among LRD donors there were 7 sets of identical twins, 92 HLA-identical siblings, 608 pairs mismatched for one HLA haplotype, and the remainder were mismatched for both HLA haplotypes with various antigen compatibilities. Among the 147 LURD there were 67 (46%) spousal pairs, 43 (29%) friends, 19 (13%) family members by law, and 18 (12%) other or unknown.

Table 1

Table 1

Table 2

Table 2

LURD donors and recipients were significantly older than LRD donors and recipients, respectively (P =0.0001) (Table 3). There were 627 females (55%) and 521 males (45%) among all LD donors. The proportions of female donors in the LRD and LURD groups were the same (55%). A significantly higher proportion of LURD allograft recipients were male (71%) when compared to LRD recipients (57%) (P =0.0013) (Table 3). There were significant differences in the donor and recipient gender pairings between LURD and LRD (P =0.0001). Compared with the LRD group, there was a greater proportion of female-to-male and a smaller proportion of female-to-female LURD transplants (Table 4). Wife-to-husband donations accounted for 69% (n=46) of spousal donations while there were 21 (31%) husband-to-wife transplants.

Table 3

Table 3

Table 4

Table 4

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.

Table 5

Table 5

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DISCUSSION

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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