CTS Collaborative Transplant Study
Dear Colleague
The donor relationship is known to be one of the most important factors that influences the outcome of kidney transplants. A distinction is usually made only between deceased and living donation although the living donors can also be divided into “genetically related” and “genetically unrelated”. Figure 1 illustrates the changes in the distribution of donor relationship in kidney transplants registered in the CTS during 1990–2020. First kidney-only transplantations that were performed in adult recipients from adult donors were considered. After a continuous increase of transplants from living donors from 1990 to around 2010, a decrease has been visible since 2015, a trend which is evident in many countries.
As is well known, one focus of the scientific research of CTS has been the influence of HLA compatibility on the outcome of kidney transplants. Due to its beneficial use in allocation and the greater number of performed transplantations, the impact of HLA compatibility has been studied mainly for deceased donors. In a fundamental paper entitled "The Risk of Transplant Failure With HLA Mismatch in First Adult Kidney Allografts 2: Living Donors, Summary, Guide" (doi: 10.1097/TXD.0000000000000664), Williams et al analyzed in 2017 the influence of HLA matching on more than 60,000 living donor kidney transplants from the UNOS registry. For this newsletter, we took a closer look at the impact of HLA compatibility on transplants from living related donors reported to CTS. The distribution of the degree of relationship among living related donors is illustrated in Figure 2.
Around half of the transplants from living related donors are from siblings (51.8 %) and around a third from parents (33.9 %). The subgroup of “Other related” includes cousins (2.7 %), nephews (1.4 %), aunts (1.0 %), uncles (0.7 %) and grandparents (0.1 %). As was to be expected, the two largest subgroups, namely siblings and parents, differ strongly in terms of recipient and donor age (Figure 3A and B). In case of living related donors, an analysis of HLA compatibility with multivariable statistical methods in mixed populations could be viewed critically since only a maximum of 3 HLA-A+B+DR mismatches is possible in transplants from parental or offspring donors as opposed to 0 – 6 in sibling donor transplants (Figure 3C).
Therefore, the 25,691 sibling and the 16,483 parental transplants were analyzed separately. In both cases, there is a significant influence of HLA-A+B+DR compatibility on graft survival (Figure 4).
In sibling transplants, the gap between 0 and >0 mismatches is remarkably large. After 12 years, graft survival with zero mismatches is more than 10 percentage points better than with 1 – 6 mismatches and among the 1 – 6-mismatched transplants, the survival of less favorably matched transplants with 4 – 6 mismatches is 3 percentage points lower than that of well-matched transplants with 1 – 3 mismatches (P = 0.021). In parental transplants, in which only a maximum of 3 mismatches is possible, the Kaplan-Meier curves do not diverge before year 5 and the well-known long-term effect of HLA mismatches becomes clearly evident only after the 5th post-transplant year.
In addition to its positive influence on long-term graft survival, a clear impact of HLA matching can also be demonstrated in the Kaplan-Meier analyses of rejection treatments during the first post-transplant year (Figure 5). 10,198 sibling and 7,102 parental transplants were analyzed. Similar to the findings on graft survival, three conclusions can be drawn:
These findings altogether indicate that HLA incompatibility influences the outcome also in transplants from living related donors and should be considered in clinical decision making, especially in the selection of appropriate immunosuppressive regimens and post-transplant surveillance of the graft.
I would like to finish with a personal note as this will most likely be the last CTS Newsletter I am addressing to you. On June 9, I was appointed to the European Research Area (ERA) Chair of the Transplant Immunology at the Koç University in Istanbul, a HORIZON 2020 project supported by the European Union. Starting September 1, I will try to establish a "Transplantation Immunology Research Centre of Excellence (TIREX)" in Turkey with the aim to connect the ERA with the Middle-East countries. The authorities in Heidelberg are currently discussing in which form CTS, the largest database in the field of organ transplantation, will best be continued. I am sure a good solution will soon be announced. I will still be available for assistance and advice as needed and will, of course, remain dedicated to CTS, also with my new center, and do my best to accomplish the ongoing projects with the help of the experienced CTS staff and my colleagues in Heidelberg.
It was a great honor to work with you and coordinate CTS during the last six years. I thank you all for your trust and generous support.
With my best personal regards,
Caner Süsal