Access to Kidney Transplantation after a Failed First Kidney Transplant and Associations with Patient and Allograft Survival: An Analysis of National Data to Inform Allocation Policy

Abstract

Background and objectives: Patients who have failed a transplant are at increased risk of repeat transplant failure. We determined access to transplantation and transplant outcomes in patients with and without a history of transplant failure.

Design, setting, participants, & measurements: In this observational study of national data, the proportion of waitlisted patients and deceased donor transplant recipients with transplant failure was determined before and after the new kidney allocation system. Among patients initiating maintenance dialysis between May 1995 and December 2014, the likelihood of deceased donor transplantation was determined in patients with (n=27,459) and without (n=1,426,677) a history of transplant failure. Among transplant recipients, allograft survival, the duration of additional kidney replacement therapy required within 10 years of transplantation, and the association of transplantation versus dialysis with mortality was determined in patients with and without a history of transplant failure.

Results: The proportion of waitlist candidates (mean 14%) and transplant recipients (mean 12%) with transplant failure did not increase after the new kidney allocation system. Among patients initiating maintenance dialysis, transplant-failure patients had a higher likelihood of transplantation (hazard ratio [HR], 1.16; 95% confidence interval [95% CI], 1.12 to 1.20; P<0.001). Among transplant recipients, transplant-failure patients had a higher likelihood of death-censored transplant failure (HR, 1.44; 95% CI, 1.34 to 1.54; P<0.001) and a greater need for additional kidney replacement therapy required within 10 years after transplantation (mean, 9.0; 95% CI, 5.4 to 12.6 versus mean, 2.1; 95% CI, 1.5 to 2.7 months). The association of transplantation versus dialysis with mortality was clinically similar in waitlisted patients with (HR, 0.32; 95% CI, 0.29 to 0.35; P<0.001) and without transplant failure (HR, 0.40; 95% CI, 0.39 to 0.41; P<0.001).

Conclusions: Transplant-failure patients initiating maintenance dialysis have a higher likelihood of transplantation than transplant-naïve patients. Despite inferior death-censored transplant survival, transplantation was associated with a similar reduction in the risk of death compared with treatment with dialysis in patients with and without a prior history of transplant failure.

Keywords: Allografts; Graft Survival; Homologous; Renal Replacement Therapy; Transplant Recipients; Transplantation; United States Renal Data System; Waiting Lists; dialysis; kidney transplantation; mortality risk; transplant outcomes.

Graphical abstract

Figure 1.

Assembly of incident ESKD and transplant-failure patient cohorts. The incident ESKD patient cohort consists of 1,426,677 patients and the failed transplant patient cohort consists of 27,459 patients.

Figure 2.

Access to transplantation in incident ESKD and Transplant Failure patients. Estimated cumulative incidence of deceased donor transplantation (A) and activation to the waitlist (B) among 1,426,677 patients with incident ESKD (solid line) and 27,459 patients with a history of transplant failure (dotted line), truncated at 10 years. (C) Estimated cumulative incidence of deceased donor transplantation after waitlisting among 322,267 patients with incident ESKD (solid line) and 12,021 patients with a history of transplant failure (dashed line). The curves in A and B are representative of a cohort characterized by the mean of the variables used in multivariable Cox models, which included adjustment for age, sex, race, cause of ESKD, body mass index, year of first incidence of ESKD or first transplant failure, medical insurance, employment status, and the comorbid conditions. Curves in (C) are representative of a cohort characterized by the mean of the variables in a multivariable Cox model that included adjustment for age, sex, race, cause of ESKD, body mass index, year of first incidence of ESKD or first transplant failure, ABO blood group, and PRA.

Figure 3.

The difference in adjusted patient survival and death-censored allograft failure among (A) first (n=127,670) and (B) second deceased donor transplant recipients (n=3848). Curves were developed from Cox models adjusted for age, sex, race, cause of ESKD, body mass index, type of medical insurance, year of transplant, congestive heart failure, peripheral vascular disease, cerebrovascular disease, atherosclerotic heart disease, chronic obstructive pulmonary disease, alcohol or drug dependencies, tobacco use, the inability to ambulate, PRA, and KDPI.

Figure 4.

The adjusted relative risk of death in first deceased donor transplant recipients (n=127,670; solid curve) and second deceased donor transplant recipients (n=3848, dashed curve) compared with patients waitlisted for transplantation (dotted line with relative risk =1.0). The reference group for the first transplant recipient includes 322,267 patients waitlisted for a first transplant, and the reference group for second transplant patients includes the 12,021 patients waitlisted for a second transplant. Transplant recipients in each group were compared with waitlisted patients from the same group who had been on dialysis for equal lengths of time but who had not yet received a first or second deceased donor kidney transplant. The multivariable model included adjustment for recipient age at waitlisting, sex, race, cause of ESKD, body mass index, year of waitlisting, comorbid conditions, insurance type, and employment status. The long-term adjusted risk of death was lower in both first and second transplant recipients, but the relative risk reduction associated with transplantation was greater among second transplant recipients.