Country-specific sex disparities in living kidney donation.

There are many sex (and gender) related considerations to be taken into account when providing care for patients awaiting an organ transplant. When on dialysis, women are less likely to be waitlisted for kidney transplantation and to receive a deceased [1, 2] or living donor organ [3], while in reverse, more women than men are living kidney donors [4]. Country-specific analysis might reveal further inequalities in the process of kidney donation that place women at a disadvantage. Here we analysed the sex distribution among living kidney donors and recipients in various countries and compared them with the countries’ general population sex distribution.

SEX DISTRIBUTION OF DONORS AND RECIPIENTS IN LIVING KIDNEY DONATION

We examined 16 studies reporting the sex distribution in living kidney donation, mostly summarized in a review by Carrero et al. [4] and provided in Table 1. These were single-centre experiences (China, UK, Egypt, India, Iran, South Korea, Nepal, Russia and Turkey), national registries (Thailand, Norway, Oman and Switzerland), other sources (German Foundation of Organ transplantation, US Scientific Registry of Transplant Recipients) and an assembly from countrywide transplant centres (Nigeria). In the study from Russia, only related donors were analysed, while in the study from Norway, only first grafts were included. Donor sex was not reported in two studies (Egypt and Nigeria). Among 36 666 living kidney donations from 14 countries, 45.4% of donors were men and 54.6% were women, while for recipients, 59.7% were men and 40.3% were women. When weighted with the population size of each country [5], the donor distribution consisted of 35.9% men and 64.1% women, and for the recipients, of 78.3% men and 21.7% women, although not all studies were likely to be population representative. Six out of 14 studies reported a women donor proportion above 60%. Women donor rates equal to or below 50% were observed in Iran, South Korea, Thailand and Oman.

Table 1.

Sex distribution in living kidney donation by country

	China	UK	Egypt	Germany	India	Iran	South Korea	Nepal	Nigeria	Norway	Oman	Russia	Switzerland	Thailand	Turkey	USA
Reference	Liu,	Peracha,	Soliman,	Biller-Andorno,	Bal,	Ghods,	Kwon,	Chalise,	Arogundade,	Øien,	Mohsin,	Goryainov,	Thiel,	Noppakun,	Mıhçıokur,	Kayler,
	2013	2016	2015	2002	2007	2003	2004	2010	2011	2005	2007	2016	2005	2015	2019	2003
Total donations, N	139	713	74	380	682	1500	614	35	143	1319	198	271	631	2063	1611	26 510
Female recipients, %	20	39	26	38	11	37	31	29	23	37	38	42	36	38	26	43
Female donors, %	69	55	n/a	64	66	22	42	71	n/a	58	50	60	65	49	58	56
Expected donor pool[a] (female, %)	61.0–76.0	51.4–58.6	n/a	59.1–68.6	62.4–69.4	20.0–24.1	38.2–45.9	54.8–83.2	n/a	55.4–60.6	43.2–56.8	54.2–65.6	61.3–68.6	46.9–51.1	56.0–60.0	55.4–56.6
General population (female, %)	48.62013	50.72016	49.52015	51.22002	48.02007	49.12003	49.82004	50.82010	49.42011	50.42005	43.42005	53.72016	51.12005	51.22015	50.62019	50.72003
Non-tobacco users (female, %)	65.62012	51.82016	62.72014	53.92007	59.42007	56.12007	66.12007	64.12010	51.92010	52.02007	48.12007	64.02016	53.92007	65.42014	59.12018	56.32007
Non-obese (female, %)	48.32013	50.02015	43.12016	51.12002	47.62007	45.92003	49.52004	50.32010	47.82011	49.92005	41.02005	49.82015	51.92005	49.52015	44.52015	46.02003
No CVD (female, %)	48.12013	50.92016	49.82016	51.22002	48.12007	49.42003	49.62004	51.02010	49.42011	50.22005	43.62005	52.72016	51.02005	51.12015	49.92019	50.52003
No diabetes mellitus (female, %)	48.92013	51.62016	49.52016	51.12002	48.12007	49.12003	50.02004	51.02010	49.42011	50.82005	43.62005	53.42016	51.32005	51.22015	50.12019	51.02003
No CKD (female, %)	47.62013	50.32016	49.02016	50.22002	48.02007	48.72003	49.32004	50.82010	49.32011	50.02005	43.12005	52.92016	50.02005	50.72015	49.42019	49.72003
Employed (female, %)	44.32013	46.82016	20.22015	44.52002	25.02007	16.82003	40.92004	49.62010	45.92011	47.82005	22.22005	48.62016	45.02005	45.72015	32.32019	46.02003
DOI	https://doi.org/10.1111/ctr.12003	https://doi.org/10.6002/ect.2015.0150	https://doi.org/10.7537/marslsj120315.03	https://doi.org/10.1023/a:1016053024671	https://doi.org/10.1016/j.transproceed.2007.08.089	https://doi.org/10.1016/j.transproceed.2003.09.019	https://doi.org/10.1016/j.transproceed.2004.07.046	PMID: 20427894	https://doi.org/10.1038/kisup.2013.23	https://doi.org/10.1093/ndt/gfh696	https://doi.org/10.1016/j.transproceed.2007.04.016	https://doi.org/10.17116/hirurgia2016662-67	https://doi.org/10.1016/j.transproceed.2004.12.279	https://doi.org/10.1111/nep.12378	https://doi.org/10.6002/ect.MESOT2018.P109	https://doi.org/10.1034/j.1600–6143.2003.00086.x

Expected proportion of sex in the donor pool given as intervals (= expected sex distribution in the country's donor population, derived by the observed sex distribution of donors leading to an insignificant chi-squared test if the true, unknown distribution would be compared to the observed distribution). General population = sex distribution of the respective country in the year of the donor statistic. Red: the proportion of women in the general population was lower than the expected donor pool. Orange: the proportion of women in the general population was higher than the expected donor pool. Green: the proportion of women in the general population was compatible with the expected donor pool. Two studies were excluded because living and deceased donors were not discriminated (Tunisia: https://doi.org/10.1016/j.transproceed.2008.12.030 and Saudi Arabia: PMID: 18 202 511). CKD = chronic kidney disease; CVD = cardiovascular disease.

LIVING KIDNEY DONATION IS SHIFTED TOWARDS WOMEN AND VARIES BY COUNTRY

Based on the observed sex distribution of kidney donors in each study, we calculated intervals for the sex distribution of the ‘expected donor pool’, assuming equal donation rates of men and women within that pool. The obtained intervals represent ranges of sex distributions within which a chi-square test, testing a difference between expected and observed distribution, would be statistically insignificant, i.e. men and women in this theoretical ‘expected donor pool’ are equally likely to donate. If the sex distribution of the country's general population from the respective year [5] was within the intervals of the expected donor pool, we interpreted this result as unbiased kidney donation. Our analysis revealed that in 10 out of 14 studies, women were over-represented in the expected donor pool, compared with the proportion of women within the general population of the corresponding country (marked as red columns in Table 1). Oman was the only country where the expected donor pool was in line with the country's sex distribution, thus men and women were equally likely to donate. In only 3 out of 14 countries (Iran, South Korea and Thailand), we observed donation rates that were shifted towards men. The fact that financial compensation for kidney donation is legal in Iran is a possible explanation for this exception [6, 7].

POTENTIAL MECHANISMS LEADING TO BIASED LIVING KIDNEY DONATION

Besides biological causes, socio-cultural, socio-economic and psychological factors are possible explanations for the observed sex disparity among kidney donors. The sex distributions of some potential biological causes for this disparity (and of smoking, which may be a socio-cultural risk factor for disease) are listed in Table 1 for each country. Although a thorough interpretation here is beyond the scope, the absence of biological risk factors that might prevent kidney donation was not genuinely shifted towards women. This observation was especially notable for kidney disease itself, which is generally more prevalent among women than men, although it is well known that more men than women undergo kidney replacement therapy by dialysis [4]. The absence of tobacco use was clearly shifted towards women in all countries, and women were much less frequently employed than men in all of the examined countries except Nigeria. The latter two disproportions might be important contributors to the preponderance of kidney donation by women.

Examining individual donor pools, Zimmerman et al. observed that among acceptable donors more women proceeded to donation, and that the excess of women donors was influenced by the predominance of women among spousal donors rather than immunological or medical exclusion criteria [8]. A greater imbalance among spousal donors was also seen in transplantation registries from the USA [9] and Norway [10]. It remains a possible explanation that fewer men are potential donors to their woman partners than the other way around due to economic reasons, sensitization to the husband's antigens or simply better health of women [11]. Examining the total donor pool, a previous population-based analysis showed that after adjusting for possible explanatory factors like differences in the need for kidney replacement therapy, women still had a 44% higher incidence of donation (31% in living related donation) and decline in income had a greater effect on donation from men than women [12].

The process of decision-making in living kidney donation is complex and includes, besides biological boundaries, also themes of compelled altruism, inherent responsibility, accepting risks, family expectation, personal benefit and spiritual confirmation [13]. It is possible that women’s gender roles, empathy and altruistic behaviour contribute to greater living kidney donation in women [11]. Also, fewer men might proceed to kidney donation due to economic responsibility in the family, which might be influencing donation in Iran [14], where it can be financially compensated.

LIMITATIONS AND OUTLOOK

Our analysis is limited by the possibility that the sex distribution within a country might not accurately depict the distribution within the true donor pool and that the time period of different research studies from the 14 countries analysed ranges from 2003 to 2019. Equalling 16 years, such a large time span may make for an unfair comparison, especially with the increased public awareness and promotion of organ donation. However, we would like to point out that the purpose of the present analysis is not to judge any country's organ donation practice. As a further limitation, we also could not adjust our analysis for influential variables such as age, health and the varying comorbidity burden across the sexes, because we did not request access to the original datasets that we included in Table 1. In future research, it would be interesting to examine whether the most prominent modifiable variables that were identified for women (absence of smoking and employment) can perhaps partly explain some sex disparities in living kidney donation. Also, the psychological requirements for a kidney donor should be compared between the different countries in light of sex and gender topics.

In conclusion, the female-to-male donor rate was disproportionately high in relation to the sex distribution in most countries. We assume intertwined sex (biological) and gender (social/cultural) influences and a great impact of socio-economic, socio-cultural and psychological factors, as we identified greatly varying international proportions of woman kidney donors compared with men. Among the research opportunities that might be able to shed further light on sex and gender disparities in living kidney donation, we suggest that input from patients themselves could be the most promising and least explored so far.