CTS Collaborative Transplant Study
Dear Colleagues,
The international Collaborative Transplant Study (CTS) has collected data on kidney transplants since 1982, heart transplants since 1985, and liver, lung, and pancreas transplants since 1988, with the largest data set including kidney transplants (≈650,000), followed by liver (≈130,000) and heart transplants (≈70,000). In CTS publications, but also in the literature, only few analyses were done comparing transplant outcomes of these different organs, most often for the analysis of post-transplant malignancies such as in the paper by G. Opelz and B. Döhler on lymphomas, published in 2004 (doi: 10.1046/j.1600-6143.2003.00325.x). In this newsletter, we would like to present some comparative analyses of patient mortality in kidney, liver, and heart transplantations.
Figure 1 includes all adult patients enrolled in CTS who received a kidney, liver, or heart transplant from an adult deceased donor for the first time during 2000–2021. Multiorgan transplants were excluded. The figure shows significantly higher mortality in liver and heart transplant recipients than in kidney transplant recipients. Importantly, the differences are mainly observed in the first post-transplant year, whereas mortality rates (i) differ little after the first year and (ii) are approximately constant throughout follow up to year ten. This is particularly well illustrated in Figure 2, for which a logarithmic ordinate was used, whereby constant rates are indicated by straight lines. The slopes indicate the half-life times.
It is evident that the half-life from year one to ten for renal transplant recipients is only slightly better than that of liver or heart recipients. It must be considered, however, that graft failure without timely retransplantation after heart or liver transplantation often results in death, whereas a patient with a failed renal transplant usually returns to life-saving dialysis.
In the CTS, in case a transplanted patient dies, the cause of death is registered on the basic follow-up questionnaire (three months, six months, one year and then annually after transplantation). In the CTS database, for the kidney transplant cohort the cause of death is unknown/not reported during the first ten follow-up years for 21% of patients, for the liver transplant cohort for 11%, and for the heart transplant cohort for only 8%. For the present analysis, we classified the causes of death in five categories according to ICD-10: graft failure, infectious diseases (A00-B99), diseases of the circulatory system (I00-I99), malignant diseases (C00-C96), and other diseases.
As one can see in Figure 3, graft failure does not play a major role as cause of death in renal transplantation. For heart transplant recipients, the proportion of graft failure as a cause of death is significantly higher than for liver transplant recipients, and this cause of death decreases markedly after the first year for both organs. For all three types of transplants, infections are by far the most common cause of death in the first post-transplant year. From the second post-transplant year onwards, death due to malignant disease accounts for the largest proportion in liver transplant patients, whereas diseases of the circulatory system as the cause of death are most often seen in heart transplant recipients.
From previous analyses we know that important factors influencing mortality include the patients' geographic origin, race, age, and gender. The majority of patients analyzed here were from Europe (kidney 76%, liver 90%, heart 84%), so no meaningful further analysis was possible in this regard. The three patient cohorts were very similar in terms of patient age. The median and interquartile ranges are: kidney 53 [43–62], liver 54 [47–60], and heart 54 [44–60] years. Greater differences were seen with regard to the sex of the patients: more than one-third (36.9%) of kidney transplant patients, compared to 31.3% of liver transplant patients and less than one-quarter (22.1%) of heart transplant patients were women. Detailed analyses related to sex are very complex because comprehensive data from normal non-transplant patient populations for specific causes of death are rarely available.
In addition to the proportions of different causes of death within each cohort shown in Figure 3, comparisons of cumulative incidences are also of interest. Although Figure 3 shows that infections account for 42% of the causes of death in the first year after kidney transplantation, Figure 4 reveals that death due to infection is much more frequent after heart and liver transplantation (left figure). However, as with all-cause mortality, the incidences are nearly the same after the first post-transplant year (right figure).
The high proportion of over 30% of malignancies as cause of death in liver transplant patients after the first year shown in Figure 3 may be attributed to the fact that hepatocellular carcinoma is the second most common reason for liver transplantation. This is supported by data shown in Figure 5, where the analysis for the patients without pre-transplant malignancies (right figure) is presented in addition to the cumulative incidence of malignant deaths of all patients (left figure).
Altogether, these data show interesting differences in cause of death for the three different types of organ transplants that were analyzed. Perhaps the most intriguing finding is the strikingly higher incidence of death from infection during the first post-transplant year in liver and heart recipients as compared to kidney recipients. Differences in type and dose of immunosuppression were analyzed based on the CTS data and did not reveal a conclusive answer. More detailed research might yield important information in the future.
The next shipping date of Serum and DNA for the Biomarker Studies is
January 15, 2024.
As the year draws to a close, we would like to thank you all cordially for your continued support. Significant structural changes of the CTS are planned for 2024 to open novel scientific perspectives and offer you further opportunities for collaborative works based on the extensive CTS database.
Best wishes,
Hien Tran
for your CTS Team in Heidelberg