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.

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.

Micro- and macrovascular complications and risk factors for foot ulceration and amputation in individuals receiving dialysis with and without diabetes.

INTRODUCTION: This study examined the prevalence of microvascular and macrovascular complications in people receiving dialysis with and without diabetes and investigated independent risk factors for foot ulcers and lower-extremity amputations. METHODS: We performed a cross-sectional study of 119 individuals with diabetes and 219 individuals without diabetes receiving chronic dialysis during June 2019 at the Department of Nephrology, Rigshospitalet, University of Copenhagen, Denmark. Effects of diabetes and other risk factors were assessed by log-binomial regression. Prevalence data were compared with a historical control group of 38 individuals with diabetes receiving dialysis examined in 2004 in the same department. RESULTS: We found that persons with diabetes had a twofold higher risk ratio of current (unadjusted risk ratio 2.2 [95% CI 1.1, 4.7]) and previous foot ulcer (2.5 [1.7, 3.7]) and a fourfold higher risk ratio of lower-extremity amputation (4.2 [2.1, 8.6]) in comparison with persons without diabetes (all p < .05). Furthermore, persons with diabetes had a 70% increased risk ratio of myocardial infarction (1.7 [1.0-2.8], p = .041). In multivariable-adjusted analysis, current foot ulcer was independently associated with previous foot ulcer (adjusted risk ratio 4.0 [95% CI 1.8, 8.9]), while lower-extremity amputation was independently associated with diabetes (3.8 [1.8, 8.2]) and male sex (4.1 [1.5, 11.3]) (all p < .01). CONCLUSIONS: Individuals with diabetes receiving dialysis had a higher prevalence of foot ulcer, lower-extremity amputation and myocardial infarction compared to individuals without diabetes. Previous foot ulcer was the most important risk factor for current foot ulcer, while diabetes and male sex were important risk factors for lower-extremity amputation.

Classification of death causes after transplantation (CLASS): Evaluation of methodology and initial results.

Correct classification of death causes is an important component of transplant trials.We aimed to develop and validate a system to classify causes of death in hematopoietic stem cell (HSCT) and solid organ (SOT) transplant recipients.Case record forms (CRF) of fatal cases were completed, including investigator-designated cause of death. Deaths occurring in 2010 to 2013 were used for derivation; and were validated by deaths occurring in 2013 to 2015. Underlying cause of death (referred to as recorded underlying cause) was determined through a central adjudication process involving 2 external reviewers, and subsequently compared with the Danish National Death Cause Registry.Three hundred eighty-eight recipients died 2010 to 2015 (196 [51%] SOT and 192 [49%] HSCT). The main recorded underlying causes of death among SOT and HSCT were classified as cancer (20%, 48%), graft rejection/failure/graft-versus-host-disease (35%, 28%), and infections (20%, 11%). Kappa between the investigator-designated and the recorded underlying cause of death was 0.74 (95% CI 0.69-0.80) in derivation and comparable in the validation cohort. Death causes were concordant with the Danish National Death Cause Registry in 37.2% (95% CI 31.5-42.9) and 38.4% (95% CI 28.8-48.0) in the derivation and validation cohorts, respectively.We developed and validated a method to systematically and reliably classify the underlying cause of death among transplant recipients. There was a high degree of discordance between this classification and that in the Danish National Death Cause Registry.

Survival Benefit in Renal Transplantation Despite High Comorbidity.

BACKGROUND: The age and degree of comorbidity among transplant candidates is increasing. Knowledge of survival benefit in relation to recipient age and comorbidity is important, considering the scarcity of organs available for transplantation. The aim of the present study was to analyze the chances and survival benefit of transplantation among patients in different age groups and with different degrees of comorbidity score at the time of entering the waiting list. METHODS: Data from the Danish Nephrology Registry and Scandiatransplant were merged. Charlson Comorbidity Index scores were derived from the National Danish Admissions Registry. Study period is from January 1, 1995, to December 31, 2011. A multistate model was used to analyze the chance of having a renal transplantation and the effect of transplantation in different patients groups. RESULTS: Patients older than 65 years and patients with high comorbidity score had a decreased chance of being transplanted. However, if patients older than 65 years were transplanted with deceased donor, the mortality risk was reduced by 55% (hazard rate, 0.45 (0.26-0.75). In patients with a comorbidity score of 5 or greater, receiving a deceased donor transplant reduced the mortality risk by 72% (hazard rate, 0.28 (0.20-0.39). The overall survival benefit was 62% versus 70% in deceased versus living donor transplanted patients. CONCLUSIONS: Poor health and old age reduced the chance of being transplanted. However, patients older than 65 years and patients with high comorbidity still had a survival benefit from renal transplantation.

Changes in causes of death and risk of cancer in Danish patients with autosomal dominant polycystic kidney disease and end-stage renal disease.

BACKGROUND: With the improved prognosis in patients with autosomal dominant polycystic kidney disease (ADPKD), causes of death and the risk of cancer might have changed. This was investigated in a Danish population with ADPKD and end-stage renal disease (ESRD) between 1 January 1993 and 31 December 2008. METHODS: Data were retrieved from three Danish national registries and a total of 823 patients were identified of which 431 had died during the study period. The 16 years were divided into two 8-year periods and the causes of death were divided into six categories: cancer, cardiovascular, cerebrovascular, infection, other and unknown. RESULTS: Cardiovascular disease was the major cause of death. A multivariate competing risk model comparing the two 8-year periods, adjusted for age at ESRD, gender and treatment modality, showed that deaths from cardiovascular disease decreased by 35% [hazard ratios (HR) 0.65, P=0.008] and deaths from cerebrovascular disease decreased by 69% (HR 0.31, P=0.0003) from the first to the second time period. There were no significant changes between the time periods in death from cancer, infection, other or unknown. From the first to the second 8-year interval, the prevalence of cancer increased by 35% (P=0.0002) while the cancer incidence was stable. CONCLUSIONS: In Danish patients with ADPKD and ESRD, there was a significant reduction in cardiovascular and cerebrovascular deaths from 1993 to 2008. The prevalence of cancer increased without significant change in cancer incidence or deaths from cancer.