Trends in underlying causes of death in solid organ transplant recipients between 2010 and 2020: Using the CLASS method for determining specific causes of death

Abstract

Monitoring specific underlying causes of death in solid organ transplant (SOT) recipients is important in order to identify emerging trends and health challenges. This retrospective cohort study includes all SOT recipients transplanted at Rigshospitalet between January 1st, 2010 and December 31st, 2019. The underlying cause of death was determined using the newly developed Classification of Death Causes after Transplantation (CLASS) method. Cox regression analyses assessed risk factors for all-cause and cause-specific mortality. Of the 1774 SOT recipients included, 299 patients died during a total of 7511 person-years of follow-up (PYFU) with cancer (N = 57, 19%), graft rejection (N = 55, 18%) and infections (N = 52, 17%) being the most frequent causes of death. We observed a lower risk of all-cause death with increasing transplant calendar year (HR 0.91, 95% CI 0.86-0.96 per 1-year increase), alongside death from graft rejection (HR 0.84 per year, 95% CI 0.74-0.95) and death from infections (HR 0.86 per year, 95% CI 0.77-0.97). Further, there was a trend towards lower cumulative incidence of death from cardiovascular disease, graft failure and cancer in more recent years, while death from other organ specific and non-organ specific causes did not decrease. All-cause mortality among SOT recipients has decreased over the past decade, mainly due to a decrease in graft rejection- and infection-related deaths. Conversely, deaths from a broad range of other causes have remained unchanged, suggesting that cause of death among SOT recipients is increasingly diverse and warrants a multidisciplinary effort and attention in the future.

Fig 1. Distribution of recorded causes of death (percentages) between types of transplantation.

* Graft rejection includes one death from GvHD. ** Other organ specific and non-organ specific causes includes death from organ failure or dysfunction not caused by graft rejection, graft failure, cancer or infection, death from hemorrhage and death from other causes.

Fig 2. Cumulative incidence curves stratified by era of transplantation (2010–14 and 2015–19) for (A) death from graft rejection*, (B) death from infection, (C) death from cardiovascular disease, (D) death from graft failure, (E) death from cancer and (F) death from other organ specific and non-organ specific causes**.

* Graft rejection includes one death from GvHD. ** Other organ specific and non-organ specific causes includes death from organ failure or dysfunction not caused by graft rejection, graft failure, cancer or infection, death from hemorrhage and death from other causes.

Fig 3. Adjusted hazard ratio* of mortality according to transplant calendar year (per one-year increase).

* Adjusted for the baseline (gender, age at time of transplantation and transplanted organ) and time-updated characteristics (number of transplantations). ** Graft rejection includes one death from GvHD. *** Other organ specific and non-organ specific causes includes death from organ failure or dysfunction not caused by graft rejection, graft failure, cancer or infection, death from hemorrhage and death from other causes.