CTS Collaborative Transplant Study
Dear Colleague
As has become customary at the start of each year, all transplant outcome graphs on the CTS website have been updated, an additional year of follow up has been added. This, of course, will also affect the analysis of your own center’s data performed via the CTS website. From past experience we know that complaints about disappointing single-center statistics are usually due to incomplete reporting of data. Please make sure that transplantations from your center are reported completely because this is a prerequisite for adequate outcome analysis. You are welcome to use the CTS outcome graphs for teaching purposes or presentations at conferences. No special request is necessary.
In a recent publication in "Frontiers in Immunology" Echterdiek et al. from the Stuttgart transplant center analyzed with us the changes regarding the influence of donor age in deceased donor kidney transplantations observed in Europe from 1997–2006 to 2007–2016. (Echterdiek F, Schwenger V, Döhler B, Latus J, Kitterer D, Heemann U and Süsal C. Kidneys From Elderly Deceased-Donors − Is 70 the New 60?, doi:10.3389/fimmu.2019.02701). In this newsletter we would like to share with you several additional aspects related to the findings reported in this paper.
Figure 1 demonstrates the distribution of donor age during the transplant periods 1997–2006 and 2007–2016. The median of donor age increased from 46 to 52 years and its interquartile range from 32–57 to 40–63 years. There was a clear shift towards the use of kidneys from ≥60-year-old expanded criteria donors, an observation which deserves special attention.
The multivariable Cox regression results from Table 2 of the paper by Echterdiek et al. are illustrated graphically in Figure 2. 18–49-year-old donors from the period 1997–2006 served as reference. The core message is that, within only one further decade, death censored graft survival improved in all donor age categories to the level of the next lower donor age category in the previous decade. The hazard ratio for graft loss of kidneys from 60–69-year-old donors was, for example, 1.45 during 2006–2016, identical with the hazard ratio calculated for kidneys from 50–59-year-old donors during 1997–2006. The same improvement was also observed for kidneys from 50–59- and 70–89-year-old donors.
Following the publication of this report, we received two important comments, namely that the risks associated with transplantation of kidneys from ≥70-year-old donors might have been downplayed and that the influence of donor age on patient mortality, although included in all cause graft survival analysis, was not presented separately.
Figure 2 demonstrates that the same results were achieved with kidneys from ≥70-year-old donors during 2007–2016 as with kidneys from 60–69-year-old donors in the previous decade. This finding indicates that donor age-related allocation strategies should be reevaluated and adjusted accordingly. On the other hand, Figure 2 also shows that, compared to the reference of 18–49-year-old donors in the same decade, the relative impact of donor age remained similarly strong in all donor age categories. For example, for kidneys from 60–69-year-old donors, the calculated hazard ratio for death censored graft loss was 1.92 during 1997–2006, only slightly higher than the 1.81 (= 1.45 / 0.80) ratio during 2007–2016. This was also true for kidneys from ≥70-year-old donors; 2.53-fold higher risk during 1997–2006 and 2.40-fold higher risk (= 1.92 / 0.80) during 2007–2016.
A more challenging task is the analysis of the influence of donor age on patient survival. Most probably due to a generally practiced age-matching, donor and recipient age show a strong correlation (Figure 3a) and there is a highly significant and rather exponential influence of recipient age on patient survival (Figure 3b). For this reason, either complex Cox regressions or, when the results of Kaplan-Meier analysis are illustrated by curves, a close stratification of recipient age is necessary.
Figure 4 shows the results of the Kaplan-Meier analysis of patient survival after stratification in recipient age groups 55–64 and 65–69 years that cover the most relevant patient groups in the allocation of kidneys from elderly donors (see also CTS Newsletter 4:2016). First of all, it is remarkable that patient survival has improved greatly over the analyzed two decades in both recipient age categories. Compared to the previous decade, even with kidneys from 60–69-year-old donors, better survival rates could be achieved during 2007–2016 than with kidneys from all other younger donors. The main finding is, however, the missing impact on patient survival of donor age in the 50–79-year range during the more recent period 2007–2016 (Figure 4b: log rank P = 0.32, Figure 4d: P = 0.89). Patient survival was, in contrast, strongly impaired in recipients of kidneys from elderly donors in the previous decade.
Another question is whether there is a continuously increasing deterioration of graft survival with higher donor age or whether there is a gap in its impact related to a certain donor age group. To answer this question, kidneys from ≥50-year-old donors were divided into seven 5-year age categories (Figure 5). The analysis was restricted to first transplants during 2007–2016 and, as presented in Figure 4, to recipients aged 55–69 years. The special group of patients transplanted via the ESP program of Eurotransplant (old-to-old) was excluded.
Figure 5 demonstrates that acceptable outcome results can nowadays be achieved up to a donor age of approximately 74 years and that the 5-year death censored graft survival does not differ significantly within the donor age range 60 to 74 years (log rank P = 0.70). In contrast, death censored graft survival appears to worsen significantly when the donor is 75 years and older. However, because of the still low numbers in the decisive donor age groups, the recommendation of a precise cut-off is difficult and such a cut-off can change further in the future. Moreover, the acceptable donor age limit is, as is known, dependent on organ acceptance criteria that strongly vary among countries due to divergent organ donation rates.
The next shipping date of Serum and DNA is
June 15/16, 2020.
With sincere thanks for your continued
support and best wishes for a successful and peaceful year 2020.
Sincerely yours,
Caner Süsal