Gender Disparity in Asian-Pacific Countries: An Analysis of the ASTREG-WIT-KT Registry

INTRODUCTION According to the Global Gender Gap Index (GGGI) report of the World Economic Forum 2021, only 67%–69% of the overall gender gap has been closed in East Asia, the Pacific, and South Asian regions. None of the Asian-Pacific countries have been ranked in the top 10 list of gender-equal countries except for New Zealand. There is also emerging data showing that the coronavirus disease 2019 pandemic has widened the gender gap in health and wages within the Asian-Pacific countries including Korea, Japan, and Australia.1 Gender imbalances are noted for kidney donation and transplantation in most countries. The proportion of female living donors has been proportionally higher, and adult women with end-stage kidney disease (ESKD) are less likely to receive kidneys.2 Because the gender gap is generally larger in Asia than in Western countries while living-donor kidney transplantation (KT) prevails in Asia,3 it can be assumed that the gender gap in organ transplantation in Asian countries is also larger than that in non-Asian countries. A disproportional increase in the representation of women among living spousal donors in Asia has been another concern.4,5 To delineate if this assumption is correct, the Asian Society of Transplantation (AST) in partnership with the Women in Transplantation (WIT) held 2 virtual meetings with representation from 13 countries in 2021.6 Conclusions from those meetings can be summarized as follows: (1) there exist significant discrepancies in gender proportions for both living donors and recipients with country-specific variations7-9; (2) most participants agreed that social rather than biological factors played a major role for the observed gender disparities in Asia; and (3) a well-designed registry containing elements related to gender selection bias in organ transplantation is needed to understand the culprits for these inequities and to seek solutions. In accordance with proposals obtained from the meetings, we have developed an online registry, “Asian Organ Transplantation Registry-WIT-KT (ASTREG-WIT-KT),” for data collection and analysis of gender disparity across Asian-Pacific countries aiming to support clinical research related to gender equities in organ transplantation. Here, we presented the structure and function of ASTREF-WIT-KT and provide early data obtained from retrospective collections and analysis of 6 participating countries. MATERIALS AND METHODS Organization and Oversight To identify the status of gender equity based on collaborative database analysis aiming to improve gender equity, a steering committee was composed of members from the Asian-WIT and the Asian Organ Transplantation Registry (ASTREG). ASTREG is the official registry of the Asian Society of Transplantation. ASTREG cooperated with WIT in building and managing the ASTREG-WIT-KT platform. The steering committee is responsible for the determination of variables (Table 1), annual data collection and analysis, approving memberships, developing research projects, and improving data utilization according to the guidelines of the ASTREG. A total of 23 representatives from 22 countries were invited as members. A secure registered identification was provided to each member with data entry responsibilities. All users of ASTREG-WIT-KT are expected to comply with the ethical guidelines of the Declaration of Istanbul.10 Access to data needs to align with institutional guidelines and the ASTREG data usage agreement. TABLE 1. - Variables collected by the Asian Society Transplant Registry-Women in transplantation-kidney transplantation Categories Variables Basic data Country name, data source (national, hospital, personal, others), transplant year Transplantation activity Number of males, female recipients in total/living-donor/deceased-donor KT Relationship in living-donor KT Gender match in total/living-donor/deceased-donor KT Activities related to KT Number of males, female patients in waiting list Number of males, female in dialysis Prevalence of CKD (optional) Professional development in nephrology/transplantation Trainee in nephrology Specialist in nephrology Academic position in nephrology Ethnicity/religion Ethnicity of living donor Religion of living donor Economic status Human Development Index Gender Equity Index World Financial Forum KT, kidney transplantation. Registry Platform, Data Source, and Structure An online registry, which we called “ASTREG-WIT-KT,” was constructed using the ASTREG platform (http://ecrf.astreg.org/), a database platform affiliated with the AST and hosted by the Korean Organ Donation Registry Foundation. This registry has a panel data structure allowing users to collect longitudinal data. A total of 360 variables selected by the steering committee related to kidney donation, transplantation, waiting list, dialysis, region, self-reported ethnicity, socioeconomic status, and proportion of female professionals in nephrology were used (Table 1). Aggregated forms of data obtained from national, hospital, and personal resources were registered by designated investigators after approval from the Steering Committee. All data are deidentified, and only aggregated data were provided by representatives from each country, allowing us to waive ethical approval from individual registries. This platform also provides a predefined automated data validation system at the data input stage to prevent simple errors. Web-based data visualization is also possible through the automated data presentation program. Data sources were as follows: Australia, from Australia and New Zealand Dialysis & Transplant Registry; India, hospital data from the Institute of Kidney Disease and Research Center and Dr HL Trivedi Institute of Transplantation Sciences; Japan, national data from the committees of the Transplant Society and the Clinical Kidney Transplant Society; the Philippines, hospital data from National Kidney and Transplant Institute (Quezon city); South Korea, national data from Korean Network for Organ Sharing; and Taiwan, national data from Taiwan Organ Registry and Sharing center and hospital data from Linkou Chang Gung Memorial Hospital. Statistical Analysis We assessed the proportion of female donors, candidates, and recipients by KT type (living, deceased, and interspousal transplantation), year, and country. We used simple linear regression to analyze distribution trends over 5 y (2015–2019), stratified by countries and donor type, without adjustment. The proportion of female donors in interspousal KT was also captured. As for the waiting list, only the year 2019 was presented because of missing data or differences in collection formats. Statistical analysis was performed using IBM SPSS Statistics software (version 22.0; SPSS Inc., Chicago, IL). RESULTS To evaluate donation and transplantation activity in the “ASTREG-WIT-KT” program, 5-y retrospective KT data (2015–2019) were collected from 6 Asian-Pacific countries including Australia, India, Japan, the Philippines, South Korea, and Taiwan. The proportion of female living donors represented more than half of the donors in all participating countries except the Philippines (Figure 1A). The proportion of females was the highest in India (71.0%–81.1%) followed by Japan (62.6%–64.9%), Australia (β = −0.896; 95% confidence interval [CI], −1.449 to −0.343; P = 0.014) and Japan (β = −0.545; 95% CI, −0.957 to −0.133; P = 0.024) showed decreasing trends of female living donors over the 5-y observation period, whereas trends in other countries remained stagnant. The proportion of female spousal donors was uniformly higher than 50%, with the exception of the Philippines in 2019 (Figure 1C). Data on interspousal KT from Taiwan are not shown, as data were obtained from a single center with <5 interspousal transplants per year. In contrast, in all other participating countries, the proportion of female KT recipients was less than half of the living-donor KT. The proportion of female living-donor KT recipients was lowest in India (14.8%–19.1%) and highest in Taiwan (37.1%–48.6%) (Figure 1D).FIGURE 1.: The proportion of female (A) living-donor kidney transplantations (B) deceased-donor kidney transplantations, (C) interspousal kidney transplantations, (D) living-donor recipients, (E) deceased-donor recipients, and (F) waiting list.The proportion of female deceased kidney donors was lower than males in all participating countries (Figure 1B). The proportions of female deceased-donor KT recipients were <50% in all participating countries (Figure 1E). An increase in the proportion of female deceased-donor KT recipients during the observation period was noted only in Australia (β = 0.655; 95% CI, 0.399-0.889; P = 0.004). The waiting list data in 2019 showed that the female proportion was <40% in 4 countries (Figure 1F). Table S1, SDC, https://links.lww.com/TP/C465, shows overall male and female numbers of donors and recipients in living-donor KT, deceased-donor KT, and waiting list. DISCUSSION Reports on KT activities across the world suggest that the proportion of female living donors is higher than males. In addition, the proportion of female spousal donors is also much higher. In contrast, the number of female ESKD patients receiving either living-donor or deceased-donor KT is relatively lower.11 Aiming to understand the culprits for gender inequities in access to transplantation, we established an online database, ASTREG-WIT-KT to study contemporary gender-specific geographical differences in transplantation and organ donation preceding the coronavirus disease 2019 pandemic. We provide data on transplantation and donation activities from 2015 to 2019 of 6 participating countries in the Asian-Pacific region. This first report by ASTREG-WIT-KT demonstrates that collaborative pooling of data on KT and donation activity by gender is feasible. Although only a small number of countries participated over a limited observation interval of 5 y, it is evident that more women come forth as kidney donors, and fewer women have the opportunity to receive a KT. Moreover, we found a substantial gender gap for living kidney donation and transplantation in most of the countries contributing data to the registry. To close the gap and promote equal rights and contributions in organ transplantation, the gender-neutral initiative of WIT strives to promote worldwide gender equity and inclusiveness in transplantation aiming to advance and inspire women transplant professionals to champion issues of sex and gender in transplantation. Inspired by WIT, many groups with the same goals have been formed in the region. Among those is the Asian-WIT, which was established in 2019 as an affiliated group of the AST. Asian countries are much more dependent on living-donor KT than Western countries.12 Family dynamics or economic factors may affect the selection of donors.13,14 In Asia, the proportion of female living donors or recipients varies greatly by region. For instance, the Chinese national registry reported on a 66.3% proportion of female living donors. In contrast, the proportion of living-donor KT recipients was 22.7% from 2010 to 2016.15 An Indian study showed the predominance of females as living donors, contributing over 70% in a single-center study with 557 living donors.16 Studies from Iraq, Iran, and Saudi-Arabia have shown that most living donors and recipients were males.17-20 Clearly, gender disparity in transplantation and donation in the context of living donation is multifactorial with biological, psychological, and economic factors affecting the gender gap. One biological reason for this gap may be that men might be less likely to be accepted as living donors related to the higher prevalence of preexisting comorbidities including diabetes and hypertension, even though men eagerly wish to donate their kidneys to women.2 Another biological reason for fewer female KT recipients may be a reduced necessity for KT in women with a slower chronic kidney disease (CKD) progression even though the prevalence of CKD is higher in women compared with men.21,22 Furthermore, women in need for a transplant may be less likely to be matched based on immune sensitization, older age, or frailty. With the advent of ABO-incompatible KT (ABOi-KT), a higher proportion of female donors became eligible for donation to their spouses. ABOi-KT from spousal donors can be considered for ESKD patients whose only potential donor is an ABO mismatched spouse.23 In the Asia-Pacific countries, the proportion of wives donating to their husbands ranged from approximately 64%–90% in 2010s.6 This trend may increase even furthermore with a global growth ABOi-KT. In Asia, the number of men receiving KT exceeds that of women.24 In addition to biological factors, socioeconomic factors must be considered as important causes of inequities in access to transplantation including attitudes emphasizing on females as caregivers, economic factors, the dependence on healthy husbands for the wellbeing of the family in addition to power imbalances related to patriarchism and low self-esteem of women. Our observation that India has the highest female donor proportions and the lowest female recipient proportions supports the notion that socioeconomic factors may contribute to the gender gap in KT. India is ranked at 140 out of 156 countries for the GGGI 2021, suggesting that discrimination against women prevails widely. The interesting observation that the proportion of female living donors in the Philippines was <50% during the 5 y studied may be explained by the high social status of women in this country. The Philippines follows a matriarchal system as a social norm. Accordingly, the Philippines was ranked 17th by the GGGI 2021.1 Notably, gender parity has already been achieved in the Philippines with 50% females in manager positions. Our analysis suggests that women also have lower access to the transplant waitlist and thus, deceased-donor KT. Although reasons for this disparity have not been fully elucidated, both biological and social factors may be at play. A national study from the US showed that the access to transplantation for women declined with increasing age and comorbidities.25 Another study revealed that women, especially those with type 2 diabetes, had lower access to the waitlist.26 Socially, age and frailty in women may more likely be perceived by healthcare personnel as a concern to withstand surgery and immunosuppression. Further studies are needed to verify these observations addressing the gender gaps in solid organ donation and transplantation. As presented by Piccoli et al,27 to understand gender disparity in KT recipients, sex differences need to be evaluated throughout the continuing care of CKD.27,28 Despite more women having CKD than men, the proportion of females on dialysis dropped to 42%–46%, further decreased to ~40% on the waiting list, and further dropped to 37%–39% for KT.2 The ASTREG-WIT-KT registry strives, therefore, to analyze the continuum of CKD care delineating regional, ethnic, and economical parameters. The registry is also designed to address biases caused by differences in time points of data collection while reducing errors occurring by collecting data prospectively. Our study also has several limitations. One of the most important challenges was related to data collection and validation. Many countries do not have a national CKD, dialysis, and transplant registry, and we therefore relied on unit-specific/on-site data from individual centers. Access to many national datasets and granular waitlist data, variables that may influence gender disparity including age, panel-reactive antibody, and socioeconomic data in addition to posttransplant outcomes data have been limited in some of the participating countries. For example, information from India and the Philippines was restricted to single-center studies and therefore raises the issue of generalizability of those findings. Among 51 Asian countries, 22 countries (43%) performed both deceased-donor and living-donor KT, 12 countries performed living-donor KT only, and 3 countries did not perform KT at all. Additionally, 14 countries did not submit their activity report to Global Observatory on Donation and Transplantation. Only 9 Asian countries including China, India, Japan, Hong Kong, Iran, Taiwan, Thailand, Singapore, and South Korea have published national transplant database–related data in English. Thus, many low-middle income countries need to establish their own national registry. Another barrier to collecting data is related to government policies on international data sharing.29 An additional limitation of our study is the challenge in data harmonization as data structure and variables differ between countries. For example, some countries have collected transplant waiting data as newly registered patients per year, whereas other countries collected registrations at a certain point in time. In Japan, the total number of waiting-listed patients were only entered in 2019. The Philippines, on the other hand, entered waitlist data in 2018 and 2019. South Korea listed the total number of waiting list from 2015 to 2019, whereas Australia collected newly registered patients on the waitlist from 2015 to 2019. Thus, a strategy is needed that adopts and anonymizes data presentation or, alternatively, uses a common data module for keeping privacy. To overcome some of these limitations, we applied an electronic case report platform. This platform made it possible to collect data from different registries over comparable time periods, within the same format, in relatively short time. Our pilot results also show that additional data related to gender disparity from other Asian and global countries can be collected and analyzed by collaboration and expanding this ASTREG-WIT-KT platform. CONCLUSIONS Here, we present data of the new ASTREG-WIT-KT registry analyzing gender-specific aspects in KT. Using this registry, we collected data over 5 y (2015–2019) in 6 participating Asian-Pacific countries as a pilot project. Despite the aforementioned limitations, we expect that the ongoing ASTREG-WIT-KT program may improve its competence by upgrading technical solutions for data collection and management to meet the needs for a robust subgroup analysis addressing not only biological factors but also a thorough analysis of cultural, economic, and social factors contributing to the gender gap in organ transplantation. ACKNOWLEDGMENTS The authors are grateful to ASTREG officers and AST office particularly, Sohyun Park, Soyoung Shin, and Jin Young Roh for their excellent administrative support to the ASTREG-WIT-KT project. The authors deeply appreciate BETHESDA SOFT for database platform construction.

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