Newsletter 3:2024

August 1, 2024

Dear Colleagues,

In the previous CTS newsletter of May 2024, we reported that graft outcomes in kidney transplantation correlated with the "World Bank's country classification by income". However, even among high-income countries, there are significant differences in graft outcomes both between countries and between transplant centers. We wondered which factors may account for these differences. Although participating centers can analyze transplant outcomes of their own patients using web-based tools integrated in the CTS Homepage (a benefit offered to the CTS participants), one of the absolutely central principles of the CTS is not to publish country- or center-specific evaluations. Therefore, in this newsletter, countries and transplant centers were grouped according to their death-censored graft survival rates and the groups (not individual countries or transplant centers) were compared for certain parameters.

Kidney transplants from deceased donors performed between 2000 and 2019 were considered. Pediatric transplants, combined transplants, and retransplants were excluded. Only centers with more than one hundred transplants from high-income countries with at least three transplant centers were included. These inclusion criteria were met by 117,267 transplants from 187 transplant centers in 16 high-income countries across four continents. The following Figure 1 illustrates the significant differences in 5-year death-censored graft survival between the country groups.

It is indeed remarkable that country group 4 had more than twice the number of graft failures compared to country group 1.

The differences between countries are, of course, influenced by political, legal, economical, and healthcare conditions, which are not captured by the CTS. Therefore, for further analyses, within each country, transplant centers were categorized into three groups: A, above-average; B, average; C, below-average death-censored graft survival rates, based on Kaplan-Meier analyses for 5-year death-censored graft survival and Cox regressions with the following confounders: year of transplantation, recipient and donor age, gender, and race, cold ischemia time, end-stage renal disease, HLA-A+B+DR mismatches, pre-transplant panel-reactive antibodies (PRA), pre-transplant dialysis duration, diabetes status, marginal donor (reasons other than age), donation after cardiac death, and initial immunosuppressive medication (induction therapy, calcineurin inhibitors, antiproliferative agents, corticosteroids). Centers that belonged to the same group were pooled and analyzed cross-nationally. Figure 2 show the results of this categorization.

The differences between the three center groups are much smaller for Graft Survival than for death-censored graft survival, but all are significant (Figure 2).

Significant differences are also evident regarding rejection treatments and hospitalized infections in the first year after transplantation (Figure 3). For hospitalized infections, there are no differences between group B and group C centers.

Using multivariable Cox regression to analyze the impact of the aforementioned confounding factors on 5-year death-censored graft survival without consideration of center categorization, the following results were obtained: The most significant influence by far is the donor’s age, followed by the underlying disease that led to the transplantation, recipient’s age, the number of HLA-A+B+DR mismatches, pre-transplant antibodies, and the year of transplantation. Only after these factors come immunosuppressive medication, cold ischemia time and pre-transplant dialysis duration.

In previous publications and newsletters from the CTS, particular attention has been given to the impact of donor age, the number of HLA-A+B+DR mismatches, and cold ischemia time, as these factors can be influenced by allocation, see for example, CTS Newsletters 1:2010, 4:2019, and 1:2020. Figure 4 shows the varying impact of these parameters across the three center categories. Comparing center categories A and C, it is noticeable that in group A, the impact of high donor age and long cold ischemia time is lower than in group C, while the impact of the number of HLA mismatches remains equally high.

In summary, even among high-income countries, there are large differences in transplant outcomes between transplant centers. Even if the negative effect of older donor age or longer cold ischemia time was reduced in transplant centers with above average transplant outcomes, the high impact of HLA-A+B+DR mismatches was consistently seen across all transplant center categories.

Announcement

During the upcoming TTS Meeting in Istanbul, Klemens Budde will present the CTS in an Educational Workshop (Registries/Databases/Repositories) on Monday, September 23, 2024. In addition, there will be an Expert Meeting at Koç University Hospital co-hosted by TIREX (Caner Süsal, Transplant Immunology Research Center of Excellence, Istanbul) and CTS on September 21, the day before the TTS Meeting starts. A registration for the Expert Meeting which is free of charge is required (https://kutirex.ku.edu.tr/news/innovative-approaches-to-immunogenetics-and-organ-transplantation). We cordially invite you to come and meet us in Istanbul.

For those of you who submit their data via the CTS software TaXi, please be aware that there is a new TaXi version (4.4.6) that can be downloaded from our homepage (https://www.ctstransplant.org/public/taxi/downloads.shtml). Centers using old TaXi versions are no longer able to upload their data.

For those of you who prefer to submit their data via electronic forms, please note that we provide – besides the forms for kidney/pancreas and liver transplants – electronic forms also for heart/lung transplants and immunosuppressive follow-up (https://www.ctstransplant.org/public/download.shtml).

The next shipping date of

Serum and DNA for the Biomarker Studies is

October 18, 2024.

Thank you for your continued support and best wishes,

Hien Tran