Newsletter 3:2014

August 15, 2014

The CTS Newsletter 2:2000, which has been accessed on the internet more than 38,000 times, addressed the topic of improving transplant success rates over the years, a trend that has been updated recently in Transplantation 2013: 95; 4-7. Graft survival curves show that the improvement in results was more impressive in earlier years, and has decreased to a relatively slow pace more recently. In fact, it is surprising that there is any continuing improvement at all, in the face of a parallel trend that we would expect to produce lower success rates, i.e. the steady increase in the age of transplant recipients and donors. Age is by far the single most influential factor affecting transplant outcome. The evolution of recipient and donor age as reported to CTS for first deceased donor kidney transplants is illustrated in Figures 1A and B.



Figure 1


For this newsletter, we have prepared an analysis of risk for graft loss during successive time periods, firstly based on the observed overall graft survival rates, and secondly considering age, the dominating risk factor, as a confounder in a Cox model. The risk for each interval is expressed as the hazard ratio (HR) based on the reference period 1985-1987 which was set at HR=1.00. First kidney grafts from deceased donors were analyzed.



Figure 2


Figure 2A shows that the risk of graft failure - without considering recipient and donor age - decreased stepwise from HR=1.00 for transplants performed in 1985-1987 to HR=0.42 for transplants performed in 2009-2011. In other words, compared to the 1985-1987 reference period, transplants performed 2009-2011 were less than half (42%) as likely to fail within the first post-transplant year. When recipient and donor age are considered, however, the risk of failure decreases even further from 1985-1987 to 2009-2011, with HR=0.25 (Figure 2B). This result shows graphically what we all have suspected for some time, namely that without the shift towards older recipient and donor age, and the associated increase in age-related risk factors, the graft survival rate after kidney transplantation would have improved even more impressively in recent years. Only one out of four grafts transplanted during 1985-1987 that failed during the first post-transplant year would have failed during the 2009-2011 interval had the distribution of recipient and donor age remained unchanged.
Even more impressive is the change in patient survival over time, with or without the confounder of recipient and donor age. Overall, the likelihood of death during the first post-transplant year has decreased from HR=1.00 in 1985-1987 to HR=0.59 in 2009-2011 (Figure 3A). Taking into account that the average age of recipients and donors has increased substantially over the years, the age-standardized analysis shows that a transplant population in 2009-2011 would have had only a 25% risk of dying compared to the patients transplanted in 1985-1987 if the age distribution had stayed the same (Figure 3B).



Figure 3


The results show similar trends for post-transplant years 2-5. Without considering recipient and donor age, the risk of graft failure decreased from HR=1.00 for transplants performed in 1985-1987 to HR=0.51 for transplants performed in 2006-2008 (Figure 4A). With the consideration of age included as a confounder, the risk declined to just HR=0.37 (Figure 4B).



Figure 4


In the analysis of patient survival, the risk of dying during post-transplant years 2-5 decreased from HR=1.00 for patients transplanted in 1985-1987 to HR=0.67 for patients transplanted in 2006-2008 (Figure 5A). When the fact that the recipient and donor age has increased over time is taken into account, the age-standardized risk of dying during post-transplant years 2-5 declines even more impressively, from HR=1.00 in 1985-1987 to HR=0.36 in 2006-2008 (Figure 5B).



Figure 5


Unfortunately, age is not a modifiable factor. The evolution of population age has affected the general non-transplant population as well as the transplant recipient and donor populations. We are observing progressively higher means and medians for recipient and donor age, a fact that we have to accept and which has, inevitably, affected transplant outcomes. The overall improvement in observed patient and graft survival rates means that other factors must have more than counterbalanced the deleterious influence of higher recipient and donor age. Most probably, factors such as improvements in immunosuppression, improved diagnosis and treatment of rejection, better control of hypertension and hypercholesteremia, improved prophylaxis, diagnosis and treatment of infection, and many other factors have played a role. In all likelihood, greater experience by transplant professionals and improvements in personnel training, as well as the availability of better infrastructure in general have also contributed to the improvement.

Thank you – as always – for your continued support of the Collaborative Transplant Study.


Gerhard Opelz