Newsletter 2:2024

May 1, 2024

Dear Colleagues,

Thanks to the voluntary and generous contribution of hundreds of transplant centers from 59 countries around the world over the last 42 years, the Collaborative Transplant Study database now comprises more than 870,000 datasets of solid organ transplants – kidney, liver, heart, lung, and pancreas. This enormous scope of the database may be considered both a blessing and a curse due to its multinational character. In the publications based on CTS data – more than thousand so far – this aspect has always had to be taken into account in statistical analyses by including geographical confounders in multivariate approaches. It was precisely the diversity of patient groups and medical practices that has enabled the discovery of numerous insights, especially regarding rare events and differences in medical cares, and provided a valuable platform for mutual learning.

A key index for characterizing the prosperity of countries has been published by the World Bank since the 1980s, called the "Country Classification by Income", which assigns countries to four groups: low, lower-middle, upper-middle, and high income. Although this classification is solely based on Gross National Income per capita and does not directly consider the quality of healthcare, we aimed to analyze its impact on transplant outcomes in this newsletter. The analyses were based on the World Bank's current classification of 2023 and we focused on transplants in the recent time period since 2010.

Figure 1 shows that in the CTS, there are no countries with low income represented. Moreover, in countries with a lower-middle income, there are no heart or lung transplants and very few liver transplants reported to the CTS.

Therefore, we focused on kidney transplants in our further investigation. For consistency, we only analyzed first kidney transplants (n = 136,422) and excluded multi-organ transplants. The countries listed in the two categories “lower-middle income” and “upper-middle income” are combined into one “middle income” category.

For both living donor and deceased donor transplants, countries with middle income exhibit significantly lower death-censored graft survival compared to countries with high income (Figure 2). The differences in death-censored graft failure risk between middle- and high-income countries were very similar for the donor sources, with a 38 % higher risk for living donors (n = 44,176) and a 40 % higher risk for deceased donors (n = 92,246) in middle-income countries compared to high-income countries (univariate Cox regression hazard ratios 1.38 and 1.40; respectively). These differences affect both short-term and long-term death-censored graft survival.

We found that there are significant differences between middle- versus high-income countries regarding factors known to have an important influence on death-censored graft survival, such as donor age. The average donor age in deceased donor transplants is only 41.4 years in middle income countries compared to 52.2 years in high-income countries. Differences in immunosuppressive medication are also noteworthy. In middle-income countries, more than a quarter of patients (26.8 %) receive a combination of a calcineurin inhibitor (tacrolimus or cyclosporine) and azathioprine, compared to only 3.1 % in high-income countries (Figure 3). Remarkable differences are also observed in terms of antibody induction: a significantly higher percentage of patients receive antibody induction – especially ATG – in middle-income countries than in high-income countries (Figure 3).

Despite the significant differences in death-censored graft failure rates between middle- and high-income countries, there are no significant differences in the incidence of rejection treatment in the first year post-transplant for patients with functioning grafts at one year for both living and deceased donors (data not shown).

The average patient age at the time of transplantation is approximately 10 years higher in high-income countries compared to patients in middle-income countries (50.4 years versus 40.3 years). Comparative analyses of mortality must therefore consider at least patient age, so we restricted our analysis to the subgroup of patients aged between 18 and 54 years as depicted in Figure 4.

Figure 4 shows that the relative differences in patient mortality between middle- and high-income countries are even more pronounced than those observed for death-censored graft survival (Figure 2). The mortality in middle-income countries is more than twice as high as in high-income countries. How precisely differences in recipient and donor age, as well as variations in medications, affect disparities in outcomes, will be examined more closely in future multivariate analyses.

As pointed out in the CTS Newsletter 4:2023, infections, especially during the first year after transplantation, and cardiovascular diseases are the most common causes of death among kidney transplant recipients. Figure 5A, using the cohort of 18–54-years old patients of first deceased donor transplants for comparison, impressively demonstrates that infections are primarily responsible for the significantly higher mortality in middle-income countries. Risk of dying due to cardiovascular diseases is also significantly higher in these countries, although less dramatically increased (Figure 5B).

Therefore, fighting against post-transplant infectious complications – possibly as a joint effort in our global community – should be a primal task in order to improve transplant outcomes especially in lower income countries.

The next shipping date of DNA and Serum Studies is

July 12, 2024.

Thank you for your continued support and best wishes,

Hien Tran