Death after Kidney Transplantation: An Analysis by Era and Time Post-Transplant

Abstract

Background: Mortality risk after kidney transplantation can vary significantly during the post-transplant course. A contemporary assessment of trends in all-cause and cause-specific mortality at different periods post-transplant is required to better inform patients, clinicians, researchers, and policy makers.

Methods: We included all first kidney-only transplant recipients from 1980 through 2018 from the Australia and New Zealand Dialysis and Transplant Registry. We compared adjusted death rates per 5-year intervals, using a piecewise exponential survival model, stratified by time post-transplant or time post-graft failure.

Results: Of 23,210 recipients, 4765 died with a functioning graft. Risk of death declined over successive eras, at all periods post-transplant. Reductions in early deaths were most marked; however, recipients ≥10 years post-transplant were 20% less likely to die in the current era compared with preceding eras (2015-2018 versus 2005-2009, adjusted hazard ratio, 0.80; 95% confidence interval, 0.69 to 0.90). In 2015-2018, cardiovascular disease was the most common cause of death, particularly in months 0-3 post-transplant (1.18 per 100 patient-years). Cancer deaths were rare early post-transplant, but frequent at later time points (0.93 per 100 patient-years ≥10 years post-transplant). Among 3657 patients with first graft loss, 2472 died and were not retransplanted. Death was common in the first year after graft failure, and the cause was most commonly cardiovascular (50%).

Conclusions: Reductions in death early and late post-transplant over the past 40 years represent a major achievement. Reductions in cause-specific mortality at all time points post-transplant are also apparent. However, relatively greater reductions in cardiovascular death have increased the prominence of late cancer deaths.

Keywords: cancer; cardiovascular disease; epidemiology and outcomes; kidney transplantation; mortality.

Copyright © 2020 by the American Society of Nephrology.

Figures

Graphical abstract

Figure 1.

Death and graft failure outcomes of all first kidney-only transplant recipients, 1980-2018.

Figure 2.

The adjusted 5-year all-cause death rate has reduced significantly over the last 40 years. Adjusted all-cause death rate (per 100 patient-years), 1980–2018. Rates adjusted for age at transplant, sex, ethnicity, duration of dialysis, donor type, cause of kidney disease, and time period post-transplant. Pt-yrs, patient-years.

Figure 3.

A reduction in death with a functioning graft was seen at all time periods post-transplants. Rates adjusted for age at transplant, sex, ethnicity, duration of dialysis, donor type, cause of kidney disease, and stratified by time period post-transplant. Pt-yrs, patient-years.

Figure 4.

The risk of death by time post-transplant exhibitis a U-shaped curve, reflecting high risk during the first 3 months post-transplant, a reduction in risk through 3–12 months and 1–5 years, followed by progressive increases in risk of death at 5–10 years and ≥10 years post-transplant. The height of the curve has fallen over successive eras. Rates adjusted for age at transplant, sex, ethnicity, duration of dialysis, donor type, cause of kidney disease, and stratified by time period post-transplant. Pt-yrs, patient-years.

Figure 5.

Cancer death match cardiovascular death beyond the first post-transplant year. Rates adjusted for age at transplant, sex, ethnicity, duration of dialysis, donor type, cause of kidney disease, and stratified by time period post-transplant. CV, cardiovascular; pt-yrs, patient-years.

Figure 6.

Cause-specific death have declined at all time periods post-transplant over the last 40 years. Rates adjusted for age at transplant, sex, ethnicity, duration of dialysis, donor type, cause of kidney disease, and stratified by time period post-transplant. CV, cardiovascular; pt-yrs, patient-years.

Figure 7.

Comparative causes of death after graft failure; cardiovascular death remain common but the rate has declined. Adjusted cause-specific death rate after graft failure, censored at retransplant, by time post–graft failure. Rates adjusted for age at graft failure, sex, ethnicity, duration of dialysis, cause of kidney disease, donor type, and duration of time with a functioning graft. CV, cardiovascular; pt-yrs, patient-years.