Increased Donor Time to Death and Kidney Transplant Outcomes

The optimal treatment for patients with end-stage kidney disease who are undergoing dialysis is a kidney transplant. Kidney transplant provides significant benefits in survival and quality of life, as well as reductions in health care costs. However, concurrent with increases in the prevalence of chronic kidney disease worldwide are increases in transplant waiting times. Only 25% of patients listed for a transplant in the United States receive a deceased-donor transplant within five years, necessitating expanding the deceased donor pool or improving the use of organs from existing donors. 

Time to death (TTD) in controlled donation after circulatory death (DCD) is a factor with the potential to expand the deceased donor pool. Currently, most international organ donation organizations (ODOs) wait no longer than one to two hours for potential donation following circulatory death; only 6.7% of US organ donation organizations routinely wait even two hours, resulting in a substantial number of viable kidneys being lost due to the strict wait times. 

More than 10 years ago, the national standard in the United Kingdom for DCD wait time was set to a minimum of three hours. Utilizing data from the UK Transplant Registry from 2013 to 20212, Samuel J. Tingle, MBBS, and colleagues recently conducted a study to examine whether TTD from withdrawal of life-sustaining treatment is associated with kidney transplant outcomes. Results were reported online in JAMA Network Open. 

The population-based cohort used data from all 23 kidney transplant centers in the United Kingdom from January 1, 2013, to December 21, 2021. Follow-up was the date of data extraction (October 2023).  

The study exposure was the duration of TTD, defined as time from withdrawal of life-sustaining treatment to donor mechanical asystole. The primary outcome of interest was recipient 12-month estimated glomerular filtration rate (eGFR; Chronic Kidney Disease Epidemiology Collaboration 2021 formula). Recipients who lost their graft prior to one year after transplant were given a nominal eGFR value of 10 mL/min/1.73 m². Secondary outcomes included the incidence of delayed graft function (defined as the need for dialysis in the first week following transplant) and graft survival (censored at death or five years).  

The cohort included 7,183 adult recipients of DCD kidney-alone transplants. Median recipient age was 56 years, 65.0% (n=4,666) were male, and 35.0% (n=2,515) were female. The participants received deceased-donor kidney transplants from 4,102 donors. The median donor age was 55 years. Median follow-up was 3.9 years.  

Median TTD was 15 minutes (range, 0-407 minutes). An estimated 5,635 transplants were performed from donors with TTD of less than 30 minutes, 663 from donors with TTD of 30 to less than 60 minutes, 582 from donors with TTD of one to two hours, 261 from donors with TTD of two to three hours, and 42 from donors with TTD of more than three hours. 

The association of TTD with recipient 12-month eGFR was assessed using a multiple linear regression model, adjusting for a wide range of factors. There was no association between donor TTD and recipient 12-month eGFR; the difference in 12-month eGFR per doubling of TTD was –0.25 (95% CI, –0.68 to 0.19; P=.27). There were associations between increasing cold ischemic time (CIT) and worsening 12-month eGFR, as well as between increasing reperfusion time (also called second warm ischemic time) and worsening 12-month eGFR. 

The association between donor TTD and delayed graft function was examined using a multivariable logistic regression model, adjusting for the same set of potential confounders. No association was observed between donor TTD and delayed graft function (adjusted odds ratio, 1.01; 95% CI, 0.97-1.06; P=.65) each time TTD doubled.  

Independent associations existed between increasing asystolic time, CIT, and second warm ischemic time and increased odds of delayed graft function. There was no association between nephrectomy time and increased odds of delayed graft function. Those findings were not changed in sensitivity analyses adjusting for year of transplant, recipient hospital, machine perfusion, and highly sensitized patients. 

The association between donor TTD and graft survival was assessed using a multivariable Cox proportional hazards regression model (censored at five years; 799 events). There was no association between TTD and graft survival (adjusted hazard ratio for graft survival, 1.00; 95% CI, 0.95-1.07; P=.92) each time TTD doubled. There were independent associations between CIT and second warm ischemic time and graft survival. There were no associations between graft survival and asystolic time and nephrectomy time. The findings were confirmed on restricted cubic spline modeling, revealing the association between donor age and graft survival to be nonlinear. 

Compared to a theoretical wait time of one hour, the UK policy of a long DCD wait time of three hours has been associated with an estimated 885 extra transplants compared to 6,298 transplants between 2013 and 2021 (14.1% increase). Compared to a two-hour wait time, the UK policy has been associated with 303 extra transplants compared to 6,880 transplants (4.4% increase). 

The researchers cited some limitations to the study findings, including the registry cohort design and the inherent potential for selection bias. 

In conclusion, the authors said, “In this cohort study of recipients of a DCD kidney, donor TTD was not associated with kidney transplant outcomes. This is by far the largest study to date on the topic, to our knowledge, and included a significant number of transplants from donors with TTD over two hours. Our results therefore challenge ODOs and transplant services internationally, most of which have maximum wait times of one to two hours. We show that meaningful increases to transplant numbers can be safely achieved by organizations that currently implement more conservative maximum wait times. We also suggest that three hours should not be used as a hard cutoff, and prolonging wait time beyond three hours should be a balance between ODO logistics and the likelihood of proceeding.” 

Source: JAMA Network Open