Gender and sex equity in organ donation and access to transplantation represent a key priority of the European Committee on Organ Transplantation of the Council of Europe (CD-P-TO). To date, the sex of donors and recipients involved in donation and transplantation activities across the Council of Europe Member States has been preliminarily investigated through the data collection undertaken by the Newsletter Transplant of the Council of Europe and a preliminary analysis on the European landscape of donors and recipients sex in solid organ transplantation was published in late 2022 [1].

According to our earlier international investigation involving 69 countries from four continents, globally men are the more frequent deceased donors, while women are the main source of kidneys and livers from living donors [1]. Furthermore, men have a greater access to transplantation compared to women. At present there is no reason to believe that, as far as the Council of Europe Member States, such differences between sex in organ donation and transplantation may be the ultimate outcome of an unfair process. However, some have previously reported that some of the differences could be the result of social roles or pressures on women [2]. Other studies involving men and women who served as living kidney donors did not demonstrate differences in psychosocial profiles or greater vulnerability to family pressure between sex [3]. In any case, men receive the majority of transplanted organs [4] in part because of a higher incidence of chronic diseases [5, 6] and because immunological factors may disadvantage women [7]. In addition, cultural and social factors, physician biases in the perception of patient frailty, as well as potential sex-based inequities of formulas used for organ allocation and transplant criteria may limit transplant opportunities for women [2, 8–12]. At this stage, the CD-P-TO felt that a more in depth collection and analysis of data disaggregated by sex would enable a better comprehension of the possible impact of sex and gender on transplant opportunities. To this end, the CD-P-TO prepared a specifically designed questionnaire aimed at supplementing the information already available through the Newsletter Transplant [13]. Such a questionnaire was applied to all CD-P-TO Member States and a detailed analysis of the new set of data collected is here provided.

The aim of the survey was to collect comprehensive data on organ donors and recipients in the CD-P-TO Member States, with a particular focus on sex. The key components of the study were composition of waiting lists, donor and recipient baseline information, sex combinations of donor-recipient pairs for various organ transplants, and the 5-years graft survival rates based on these combinations. The collated dataset refers to the year 2019, which is the latest year that was not affected by the SARS-CoV-2 pandemic.

The CD-P-TO established an ad hoc working group lead by the Italian National Transplant Centre (CNT), who prepared a questionnaire whose final version was agreed by the CD-P-TO on 7 April 2022, and formally approved in its plenary meeting held in Warsaw on 7 October 2022. The approved version of the questionnaire is appended (Supplementary Material). The questionnaire was circulated to the 39 CD-P-TO Member States and 5 Observers Countries, and was completed by national focal points already designated by the Ministries of Health at each country for the routine data collection performed for the Newsletter Transplant. CNT then compiled the information collected by the questionnaires, assessed the accuracy and level of completeness of the data provided and performed the data analysis. In cases of inconsistencies, the CNT contacted the designated focal point in each country for a final data check.

A total number of 33 countries filled in questionnaires were received. Four member states were removed from the analysis due to incomplete data (notwithstanding the extensive efforts put in place to clarify some inaccuracies or incomplete answers). Answers to questionnaires included in the analysis were provided by 6 Ministries of Health and 23 National Competent Authorities [Supplementary Table S1]. The 5-year organ survival calculation was derived from data supplied from countries with 10 transplants or more per organ type (from either living or deceased donor).

A total of 29 countries accurately completed the questionnaire and were included in the analysis. These consisted of 26 CD-P-TO Member States (Albania, Austria, Belgium, Croatia, Cyprus, Czech Republic, Denmark, Estonia, France, Germany, Hungary, Ireland, Italy, Latvia, Lithuania, Luxembourg, Moldova, the Netherlands, Portugal, Slovak Republic, Slovenia, Spain, Sweden, Switzerland, Turkey and the United Kingdom) and 3 observer countries (Armenia, Georgia and Israel). The two main CD-P-TO observer countries, namely United States and Canada, could not take part to the analysis. Furthermore, the amount of data required and the degree of details requested did not allow several Member States to participate in this analysis.

Transplantation is the most effective therapeutic option for eligible patients diagnosed with advanced or end stage organ failure. Even though countries performing organ transplantation, make the treatment accessible to all eligible patients, irrespective of sex, age and race, it has been previously reported that, compared to men, women are disadvantaged with regards to both access to active transplant waiting lists and access to transplantation after waitlisting [13–17].

Indeed, women have lower access to transplantation. In many cases, this is the ultimate outcome of unbiased circumstances that include a higher burden of diseases treatable with transplantation among men [5, 6], organ size mismatch [18] or greater difficulties in finding an immunologically compatible donor in women due to prior immunizing events [4, 7].

Nonetheless, in the context of kidney transplantation, the choice of glomerular filtration rate (GFR) estimation methods for determining access to waiting lists remains a subject of debate. Indeed, both the MDRD and CKD-EPI equations, which are commonly used to estimate GFR, are creatinine-based and thus dependent on muscle mass; consequently, they tend to underestimate GFR in women, despite adjustments also in late chronic kidney disease (CKD) stages [19, 20]. In clinical practice, awareness of the systematic underestimation of GFR in women may create diagnostic uncertainty. This is particularly evident when evaluating borderline GFR values for transplant eligibility, where such bias can delay the initiation of the evaluation process, its completion, or final access to the waiting list—steps that are less frequent in female patients [21].

With regard to access to liver transplantation, the MELD score adopted in the United States two decades ago heavily weighted creatinine, ultimately generating a negative bias for women access to transplantation. In 2008, the MELD score was modified to incorporate serum sodium (MELD-Na). However, this update failed to mitigate—and may have even exacerbated—gender disparities, with women remaining 20% less likely to receive a transplant than men [22–24]. Furthermore, women experienced higher rates of waitlist mortality or delisting due to clinical deterioration [25]. This higher attrition rate may result, at least in part, from prolonged waiting times secondary to lower calculated MELD-Na scores.

Some reports suggest that socioeconomic or cultural factors may underlie the variation in access to transplantation between sex [3, 21, 26, 27]. Furthermore, even medical biases have been described as a possible explanation for the sex-related differences in access to this treatment [4, 28–30]. Sex-related imbalances in terms of both donation and access to transplantation have also been reported when transplantation takes place using organs from living donors [15].

To study whether sex-related aspects may contribute to a potential disparity in the transplantation activity in Europe, the CD-P-TO commissioned a further in depth analysis of organ donation and transplantation across the Council of Europe member states previously conducted in 2019 [1]. Our survey eventually enabled us to have access to data from 26 of the 39 Council of Europe Member States, ultimately covering an overall population of 527.4 million European citizens (UNFPA report [31]).

The data collected confirm that, irrespective of the organ considered, men still account for the majority of the patients awaiting transplantation.

To establish whether women on the WL wait longer than men, in this study we determined the median waiting time on the WL. Our data indicate that in the Council of Europe Member States, for all the organs except for hearts, women have a longer waiting time on the WL compared to men.

As far as organ donation is concerned, our data confirm that, as previously reported, male donors make up the majority of deceased donors (DBD or DCD) in Europe and females provide the majority of kidneys from LD. Interestingly, males make up the majority of living liver donors in the Council of Europe countries.

In light of earlier reports suggesting that sex pairs may affect graft survival [21, 32], the impact of sex combinations on 5-year graft survival was analysed for organs from both deceased and living donors. As expected, 5-year graft survival of organs from living donors had a better outcome than that of the deceased counterpart. However, in our study 5-year graft survival (for organs either from deceased or living donors) did not differ when considering the different sex pair combinations. While our data confirm recent findings suggesting that, per se, the patient sex may not represent a key determinant affecting transplant outcomes [33], we cannot rule out that the impact of the limited number of cases and the duration of the observation period in our study may explain the different findings compared to earlier reports [21, 32].

We also analysed the relationship between living donors and recipients. In Council of Europe countries, the parent-to-child pair represents the most frequent combination for both LKD and LLD. The greater involvement of parents in this case is not unexpected as having a child recipient and helping a family member are amongst the most motivating factors for considering living organ donation [34].

We acknowledge that our study presents several limitations. First, the analyses were conducted on data provided by only 26 of the 39 Council of Europe CD-P-TO Member States. Second, the data provided refer to an observation period of 1 year, a condition that may not accurately reflect the routine activities of some of the countries involved. Third, the use of the median waiting time on the WL as a means to establish whether women on the WL wait longer than men does not differentiate whether patients removal from the WL is due to access to transplantation, death on the waiting list or delisting due worsening condition. Fourth, because the data were collected in aggregate form, it was not possible to perform statistical inference analyses; therefore, only a descriptive analysis could be conducted, and differences could be evaluated solely in these terms. Nevertheless, the available data allowed us to gain an overall view of the situation. In this light, a follow up study in countries able to establish the cumulative incidence of access to transplantation for patients on the active waiting list will represent an important tool to increase our knowledge on the impact of sex on the access to transplantation for women on the active WL. Eventually, the data analysed refer to the year 2019, the last year that was not impacted by the COVID-19 pandemic. Still, this is the only set of data available that explore in detail the impact of sex on transplantation activities across the CD-P-TO Member States.

In summary, altogether the data collected from 26 Council of Europe Member States and 3 observer countries suggest that, whilst men represent the majority of patients on the organ transplant waiting lists and receive the largest number of organs from deceased or living donors, at this stage there is no evidence of unfair sex-related inequities in the transplantation activities conducted in Europe. Women provide the majority of kidneys from living donors whilst men are the major source of livers from living donors. Currently, however, we are still missing the sex-associated data regarding transplantation activities taking place in many of the Council of Europe Member States. In this light, the Newsletter Transplant has now broadened its annual data collection on organ transplantation activity to include data disaggregated by sex. In any case, this analysis provides a foundation for future in-depth studies aimed at understanding biological sex disparities in organ donation and transplantation. In this regard, the CD-P-TO will continue its monitoring activity on this highly relevant topic, possibly extending its commitment beyond sex to include gender related aspects. This should allow the CD-P-TO to uncover possibly unexpected imbalances and, where relevant, release recommendations that could act as a trigger for the adoption of new national policies.