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Volume: 14 Issue: 2 April 2016

FULL TEXT

ARTICLE
Gender Disparity in Living-Donor Kidney Transplant Among Minority Ethnic Groups

Objectives: We have limited data on gender disparities between living kidney transplant donors and recipients across ethnic groups.

Materials and Methods: This was a retrospective cohort study of all living-donor kidney transplants per­formed at a single center in an ethnically diverse region of England. Data were extracted from the United Kingdom National Transplant Database and University Hospitals Birmingham electronic medical records.

Results: We analyzed 713 living-donor kidney transplant procedures that were performed from 1987 to 2014. Gender disparities were observed, with women more likely to be living donors (54.7%) and less likely to be recipients (39.4%). Most male recipients received kidneys from female donors versus male donors (70.2% vs 29.8%), whereas the proportion of men receiving kidneys from women (50.9%) and from men (49.1%) were similar (P < .001). Black, Asian, and donors from other minority groups comprised 18.7% of the donor cohort. South Asian partner-to-partner transplants (n = 22) were pre­dominantly men receiving transplants from women (90.9%) versus women receiving transplants from men (9.1%; P = .003). Male patients more commonly donated their kidney to children than to women (10.2% vs 6.4%; P = .046). South Asian donations to children were similar between males and females; however, boys exclusively received kidneys from male donors (8/8) versus from female donors (8/12).

Conclusions: Gender disparity exists in living-donor kidney transplant, with disparities more pronounced in some ethnic groups and among particular re­lationships. This finding requires targeted counseling and research to understand whether the cause is medical or sociocultural obstacles.


Key words : Ethnicity, Cultural, South Asians, Living kidney donation

Introduction

Living-donor kidney transplant is the treatment of choice for patients with end-stage kidney disease. In 2014, one thousand forty-nine and 65 living-donor kidney transplants were performed in the United Kingdom for adult and pediatric patients with end-stage kidney disease (representing 35.8% and 52.0% of all kidney-alone transplants in adults and pediatric patients).1 Methods to encourage living-donor kidney transplant in the United Kingdom are critical to bridge the gap in supply versus demand for kidneys, with the importance of boosting the rate of living-donor transplant underpinned by the current national strategy led by the National Health Service Blood and Transplant.2

However, for some patients, access to living-donor kidney transplant has been restricted by 2 important phenomena. First, kidney transplants involving living donors from the black, Asian, and minority ethnic (BAME) community remain comparably low compared with transplants involving living donors from the white community.1 This is a concern as the incidence of end-stage kidney disease is higher3 and the wait time for kidneys on the national deceased organ wait list is longer1 (because of an even greater shortage of deceased organ donors from the BAME community) in BAME communities. Second, gender disparity in living-donor kidney transplant has been well described, with women more likely to be donors and male patients more likely to be recipients.4-9 It is unclear how these 2 phenomena interact and whether gender disparities are worsened in BAME com­munities. It is also unclear whether the gender disparities observed in living-donor kidney transplant are influenced by the nature of familial versus nonfamilial relationships.

The aim of this study was to analyze all living-donor kidney transplants performed at our institution, which caters to an ethnically diverse region of England, with the working hypothesis that gender disparity is exacerbated in the context of living-donor kidney transplant in the BAME community.

Materials and Methods

This was a retrospective cohort study of all living-donor kidney transplants taking place at a single transplant center (Queen Elizabeth Hospital Birmingham) between 1987 and June 2014. Patient demographics, including gender, age, ethnicity, and relationships between donors and recipients, were obtained from the United Kingdom National Transplant Database. Data were extracted from all living-donor kidney transplants performed at our institution since 1987 and from the current active kidney wait list. Additional data on living kidney transplant donors and recipients (eg, patient religion) were obtained from the electronic medical records at University Hospitals Birmingham where available. The study, which was approved by the Ethical Review Committee of our institution, was registered with the Clinical Audit team at the University Hospitals Birmingham (audit code: CRMS-11304). All of the protocols conformed to the ethical guidelines of the 1975 Helsinki Declaration.

Statistical analyses were performed with SPSS software (SPSS: An IBM Company, version 17.0, IBM Corporation, Armonk, NY, USA). Normality of data was assessed using the Kolmogorov-Smirnov tests. Descriptive statistics were used to estimate the frequencies, means, and medians of study variables. For continuous variables, the t test and Mann-Whitney U test were used for parametric and nonparametric data. Differences between groups were assessed with 2-sided Fisher exact test or Pearson chi-square test for categoric variables as appropriate. A P value of .05 or less was considered significant.

Results

Demographics of donors and recipients
There were 713 living-donor kidney transplants conducted at Queen Elizabeth Hospital Birmingham between 1987 and June 2014. Table 1 highlights the baseline demographics of donors and recipients, with significant differences observed in some comparative markers. The 5 main relationships between donors and recipients were parent-to-child (30.9%, n = 220), partner-to-partner (27.8%, n = 198), sibling-to-sibling (27.3%, n = 195), child-to-parent (8.6%, n = 61), and friend-to-friend (2.0%, n = 14) transplants, with the remaining relationships making up 3.2% (n = 23) of the cohort. In general, most transplants were familial (n = 500) versus nonfamilial (n = 211), with 2 relationships that were not documented. We found no significant difference between men and women in regard to the likelihood of familial donation (71.5% vs 69.0%; P = .747). In transplants involving familial relationships, females comprised 53.8% and 39.8% of donors and recipients (P = .159), whereas in transplants involving nonfamilial relationships, females comprised 56.9% and 38.9% of donors and recipients (P < .001).

Donors and recipients in the BAME community
The BAME community comprised 18.1% of the living kidney donors (see Table 1). Median age of donors from the BAME community was statistically lower than the median age of white donors (39 vs 47 years; P < .001). Female members from the BAME community comprised a higher proportion of donors (53.4%) but lower proportion of recipients (40.6%), but there was no significant difference in these proportions in comparison to female members from the white cohort (55.0% and 39.1%). Members from the BAME cohort were significantly less likely to partake in familial than in nonfamilial donor-to-recipient donations versus that shown in the white cohort (67.7% vs 70.7%, P = .011). It should be noted, however, that most nonfamilial donor-to-recipient donations in our cohort were partner to partner and that, in some BAME communities (eg, South Asian), consanguineous marriages are common (although we lacked specific data regarding this).

In general, there were no significant differences in gender distribution for donor-recipient pairs when we compared white versus BAME living-donor kidney transplants: male-to-female proportion was 23.1% versus 26.0%, female-to-male proportion was 38.4% versus 36.6%, male-to-male proportion was 21.9% versus 21.0%, and female-to-female proportion was 16.6% versus 16.0%.

Gender disparity by relationship
In total, 54.6% of all donors and 39.0% of all recipients were female. In our cohort, 323 donors were men and 390 donors were women. In contrast, there were more male recipients (n = 432) than female recipients (n = 281). We found that there were more donations from women to male patients than to female patients (70.0% vs 30.0%; P < .001), whereas donations from men to female patients (50.8%) and to male patients (49.2%) were similar. Table 2 illustrates the statistically significant differences between male donors versus female donors dependent on the relationship between donors and recipients for living-donor kidney transplant.

Women were more likely to be the living donor in partner-to-partner kidney transplants (58.1%) than men (40.9%). There was no difference in the proportion of female-to-male partner donations in the white versus BAME community (58.1% vs 56.1%). However, we did observe a large discrepancy among South Asian partner-to-partner transplants (n = 22), with more women being the donor compared with that shown in the white community (90.9% vs 58.1%; P = .003).

Donations from parents to children
Parent donor to child recipient was the most common relationship for living-donor kidney transplant at our institution (n = 220) and represented 30.9% of all living-donor kidney transplants. Men were more likely than women to donate kidneys to pediatric recipients (10.2% vs 6.4%; P = .044). When compared by ethnic group, no gender differences were shown regarding parents donating a kidney to their child, with an equal split between male and female BAME parents donating to their child (15.4% vs 15.5%; P = .568). For South Asian parents, no differences were shown regarding male versus female donations to pediatric recipients (9.9% vs 9.3%). However, an interesting observation was that boys exclusively received kidneys from male donors (8/8) compared with a two-thirds split in favor of boys for female donations (8/12).

Religion
Religious affiliation was recorded as “not known” in 68.2% of kidney donors, limiting analysis of religion as a variable. However, religion was better recorded for South Asian donors with only 28.7% (n = 23) of South Asian donors having unknown religious status. Religious belief represented among South Asian donors included Islam (n = 28, 35%), Hinduism (n = 9, 11.2%), Christianity (n = 4, 5%), Sikhism (n = 15, 18.8%), and atheist/agnostic (n = 1, 1.2%). No evidence was found of any significant effect of donor religion on living-donor kidney transplant among South Asians; however, with limited numbers, cautious interpretation is needed.

Active deceased-donor kidney wait list at our institution
It is important to compare any evidence of gender disparity within the data of living kidney donors in the context of the regional kidney wait list at our institution (see Figure 1). From 459 actively waiting patients (as of March 24, 2015), 187 are female. Ethnicity of our wait list is as follows: 259 white patients, 45 black patients, 135 South Asian patients, 5 Chinese patients, 3 mixed patients, 5 unknown, and 7 other. Of 135 South Asian and 45 black patients on our kidney transplant wait list, 57 (42.2%) and 19 (42.2%) are female, with a smaller proportion (39.8%, n = 103/259) of white female patients on the wait list.

The average wait time for South Asian female patients is 1393 days versus 1041 days for South Asian males. The average wait time is 1263 days for black female patients versus 1461 days for black males. White female patients have an average wait time of 1171 days versus 1157 days for white males. Female patients are also more difficult to match than males across all ethnicity groups as determined by the matchability score. This is translated from a match count (calculated by number of donors in a pool of 10 000 that patients are blood group identical, HLA compatible, and favorably HLA mismatched [000, 100, 010, 001]) into a standardized score of easy (1-3), moderate (4-7), or hard (8-10) to match. Differences in average matchability score comparing male versus female patients were as follows: 5.0 versus 6.0 for white, 6.7 versus 7.4 for black, and 5.2 versus 7.5 for South Asian. Therefore, South Asian female patients who are presently on the deceased-donor wait list in our region have the longest wait time and most difficult matchability than all male and female patients in all other ethnic groups.

Discussion

This single-center retrospective analysis of 713 living-donor kidney transplants is one of only a few studies to explore the relationship between gender disparities, stratified by ethnicity in a multicultural region. Our study confirmed some well-known observations consistent with living-donor kidney transplant (eg, more female donors and less female recipients) but also introduced some unknown findings that merit further discussion (eg, ethnic disparity in South Asian partner-to-partner and parent-to-child donations). Religion had no significant effect on kidney donations from living donors, but this was in the context of poorly recorded religious data. Our results identify significant sociocultural (rather than religious) barriers to expansion of living-donor kidney transplant in established transplant programs, and this information should be used to enhance educational materials for potential living kidney donors from the BAME community.

With more living-donor kidney transplants, wait times for patients with end-stage kidney disease are less prolonged, and this is especially pertinent to patients from the BAME community. Our active wait list has 200 patients from the BAME community (43.5% of our kidney wait list), but these patients have a much longer wait (and more difficult matchability) than white patients in our cohort. Despite this, only 13% of our living kidney donors within the region were from the BAME community. Although this is better than the 5% deceased-donor organ rate from the BAME community nationally, it still fails to meet the needs of a growing population of BAME end-stage kidney disease patients on the deceased-kidney wait list.

Global activity in donations from living donors accounts for 41.9% of all kidney transplants performed worldwide in 2013, although with substantial geographic variation.10 For example, donations from living donors account for 93.8%, 80.6%, and 70.8% of kidney transplants performed across Asia, Arabia, and Africa versus 30.5% in Europe.10 This reflects both differences in the established infrastructure for deceased organ donation (eg, organ retrieval and allocation systems) and the underlying sociocultural issues regarding donations from deceased donors (reflecting acceptance of brain death classification11). In the United Kingdom, rates of kidney donations from living donors are better among members of the BAME community than rates of donations from deceased donors.1 This suggests that some of these residual sociocultural perceptions among the BAME community are retained from their countries of origin but may simply reflect an acceptance from BAME patients that securing a kidney from a living donor provides their best chance to overcoming the prolonged wait for kidneys.

Innovative strategies to boost kidney donations from living donors specifically targeting the BAME community have been assessed, including home visits,12 dedicated ethnic-centric Web sites,13,14 education packages in the patient’s primary language,15 and navigators through the transplant process.16 However, these studies have been conducted in minority ethnic communities in the United States, and minority ethnic communities are different in the United Kingdom (eg, South Asians, African Caribbean) from the United States (eg, Hispanics, African Americans, Asian Americans). This is a critical gap in the literature, with no studies looking at boosting kidney donations from living donors in the British population. In addition, it is unclear whether such strategies among the BAME community will overcome gender disparities that have been outlined in this analysis. Having a tailored approach to tackle gender and ethnicity obstacles, such as dedicated community-derived peer educators, may be a solution to overcome these challenges.17

Gender disparity has been observed in living-donor kidney transplant, and this appears to be unrelated to underlying medical issues in men or increased female representation in the general population.5 However, there are many confounding influences to who does and does not become an organ donor.18 For example, women have been identified as being less willing to receive a kidney from a living donor than men (58.5% vs 87.5%; P = .003), especially among the black community.8 Our analysis demonstrates significant gender disparities, especially in partner-to-partner and parent-to-child kidney transplant between South Asian donors and recipients. The explanation for this is speculative, but culture is likely to supersede any biologic factors, with the well-recognized gender discriminatory health issues among South Asians.19 South Asians have a greater tendency to have type 2 diabetes mellitus, hypertension, ischemic heart disease, and/or chronic kidney disease than the white population20; therefore, this group may be less suitable as living kidney donors in general. However, there is little evidence that any gender disparity exists in the incidence of these health issues.

In cases of partner-to-partner living-donor kidney transplant among South Asians, in 90.9% of cases, donation was from women to men. This is higher than that shown in the study by Kayler and associates, where females comprised 68% of donors in all spousal pairs,4 but consistent with previous literature conducted in South Asians that identified an 87.7% living donor rate in marriages from wife to husband.5 Of note, not all studies have identified women as more likely to be the living kidney donor. Taheri and colleagues, analyzing 16 672 living kidney donations from the Iranian national registry, identified men as being the donors and recipients in 80.0% and 62.2% of cases, with recipients more likely to receive a living kidney donation from their own gender group.21 The authors speculated on multifactorial reasons to explain the predominance of men as the living kidney donor, which included social, cultural, and economic factors.

Although it is important to encourage more male-to-female living kidney donations, we should also be mindful of literature suggesting the increased risk for allograft attrition with male-to-female kidney donations. This can arise from allorecognition of minor human histocompatibility antigens such as H-Y antigens, which are derived from the Y chromosome and have prognostic implications in donor-recipient gender mismatched hematopoietic stem cell transplants.22-24 From a kidney transplant perspective, Gratwohl and associates analyzed data from the Collaborative Transplant Study and identified that female recipients of male deceased-donor kidneys had increased risk of death-censored graft failure during the first year (hazard ratio of 1.11; 95% confidence interval, 1.04-1.19; P = .003) and between 2 and 10 years (hazard ratio of 1.10; 95% confidence interval, 1.05-1.16; P < .001).25 A separate analysis of kidney allograft recipients from the US Renal Data System identified increased risk of graft failure for female recipients of kidneys from male donors within the first year after transplant (hazard ratio of 1.12; 95% confidence interval, 1.05-1.19) but not after 10 years (hazard ratio of 1.03, 95% confidence interval, 0.98-1.07).26 Similar adverse outcomes have been observed for female recipients of organs from male donors in the context of liver,27 heart,28 and lung transplant.29 Further work is required to understand the allograft survival effects of gender mismatched kidney transplants and how ethnicity may influence the short- and long-term outcomes in this context.

There are several limitations to this study. We have no record of potential living kidney donors who came forward but were declined for medical reasons. This would allow us to confirm whether gender disparity in certain ethnic relationships is not biased against men due to greater prevalence of underlying health issues. However, Zimmerman and associates have previously found men and women were ruled out as potential donors at similar rates on the basis of basic medical conditions or blood group incom­patibility.4 In addition, Lunsford and associates speculated in their retrospective analysis that low rates of living organ donations from African Americans were more likely secondary to disparity in willingness to donate (eg, loss to follow-up) rather than medical unsuitability.30 We also lacked data with regard to consanguinity, which may have an effect on medical suitability for some BAME donors, such as those from South Asian, because consan­guineous marriages are common and leads to increased prevalence of autosomal recessive conditions.31,32 Long-term allograft survival data were not analyzed as part of this study. Although this is of interest, the purpose of this retrospective review was to explore the gender/ethnic disparities in living-donor kidney transplant rather than long-term clinical outcomes. Finally, missing data such as religious affiliation limited more comprehensive analysis of donor and recipient factors that could have had an effect on the final results.

To conclude, we found gender disparity in living-donor kidney transplant in a single center that caters to a multicultural region and identified skewed gender disparity among the BAME community that is exacerbated in selected relationships. We anticipate these results will guide clinicians and living donor coordinators and lead to appropriate counseling for patients and potential donors. Further research is required to understand whether this gender disparity reflects a greater degree of underlying health conditions prohibiting kidney donation or is symbolic of sociocultural obstacles. Living donor education programs require sensitive handling of both ethnic and gender disparity issues, although the optimum strategy to overcome social and cultural obstacles among the BAME community with regarding living (and deceased) kidney donation ultimately requires definitive evaluation and validation.


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Volume : 14
Issue : 2
Pages : 139 - 145
DOI : 10.6002/ect.2015.0150


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From the Department of Nephrology and Transplantation, Queen Elizabeth Hospital, Birmingham, United Kingdom
Acknowledgements: The authors declare that they have no sources of funding for this study, and they have no conflicts of interest to declare. Javeria Peracha was responsible for data collection, data analysis, data interpretation, drafting the article, statistical analysis, and final approval. Manvir Kaur Hayer was responsible for data collection, data analysis, data interpretation, critical revision, and final approval. Adnan Sharif was responsible for concept/design, data interpretation, drafting the article, critical revision, statistical analysis, and final approval.
Corresponding author: Adnan Sharif, Department of Nephrology and Transplantation,
Queen Elizabeth Hospital, Mindelsohn Way, Edgbaston, Birmingham, United Kingdom
B15 2WB
Phone: +1 21 371 5861
Fax: +1 21 371 5858
E-mail: adnan.sharif@uhb.nhs.uk