Differential effects of donor-specific HLA antibodies in living versus deceased donor transplant

Abstract

The presence of donor-specific anti-HLA antibodies (DSAs) is associated with increased risk of graft failure after kidney transplant. We hypothesized that DSAs against HLA class I, class II, or both classes indicate a different risk for graft loss between deceased and living donor transplant. In this study, we investigated the impact of pretransplant DSAs, by using single antigen bead assays, on long-term graft survival in 3237 deceased and 1487 living donor kidney transplants with a negative complement-dependent crossmatch. In living donor transplants, we found a limited effect on graft survival of DSAs against class I or II antigens after transplant. Class I and II DSAs combined resulted in decreased 10-year graft survival (84% to 75%). In contrast, after deceased donor transplant, patients with class I or class II DSAs had a 10-year graft survival of 59% and 60%, respectively, both significantly lower than the survival for patients without DSAs (76%). The combination of class I and II DSAs resulted in a 10-year survival of 54% in deceased donor transplants. In conclusion, class I and II DSAs are a clear risk factor for graft loss in deceased donor transplants, while in living donor transplants, class I and II DSAs seem to be associated with an increased risk for graft failure, but this could not be assessed due to their low prevalence.

Keywords: alloantibody; clinical research/practice; graft survival; kidney failure/injury; kidney transplantation; kidney transplantation/nephrology; living donor.

Figure 1

Prevalence of pretransplant HLA‐Abs and donor‐specific HLA antibodies (DSAs) in the total cohort (N = 4724). A. Venn diagram showing the prevalence of pretransplant HLA‐A/B/DR/DQ HLA‐Abs. B. Venn diagram showing the prevalence of pretransplant HLA‐A/B/DR/DQDSAs [Color figure can be viewed at http://www.wileyonlinelibrary.com]

Figure 2

Long‐term graft survival of kidney transplants according to the presence of pretransplant donor‐specific HLA antibodies (DSAs). A. Adjusted Kaplan–Meier estimates (AKME) for death‐censored graft survival according to the presence of pretransplant DSAs for the total cohort including deceased‐ and living‐donor transplants (N = 4724). B. AKME for death‐censored graft survival according to the presence of pretransplant DSAs for living‐donor transplants only (n = 1487). C. AKME for death‐censored graft survival according to the presence of pretransplant DSAs for deceased‐donor transplants only (n = 3237). All AKME were adjusted for the same covariates: recipient age (quadratic) and donor age (quadratic), donor type (living or deceased; for the total cohort only), cold ischemia time (for donation after brain death [DBD] and donation after cardiac death [DCD]), time on dialysis in years (quadratic), and induction therapy with interleukin‐2 receptor blocker [Color figure can be viewed at http://www.wileyonlinelibrary.com]

Figure 3

Impact of donor‐specific HLA antibodies (DSAs) on graft survival for deceased‐donor transplants. A. Adjusted Kaplan–Meier estimates (AKME) for 1‐year death‐censored graft survival according to the presence of pretransplant DSAs for living‐donor transplants only (n = 1487). B. AKME for 1‐year death‐censored graft survival according to the presence of pretransplant DSAs for deceased‐donor transplants only (n = 3237). C. Analysis of long‐term effect of pretransplant DSAs starting at 1 year after transplant for living‐donor transplants only (n = 1417). D. Analysis of long‐term effect of pretransplant DSAs starting at 1 year after transplant for deceased‐donor transplants only (n = 2834). E. AKME for death‐censored graft survival according to the presence of pretransplant HLA class I (A/B) and/or II (DR/DQ) DSAs for living‐donor transplants only (n = 1487). F. AKME for death‐censored graft survival according to the presence of pretransplant HLA class I (A/B) and/or II (DR/DQ) DSAs for deceased‐donor transplants only (n = 3237). All AKME were adjusted for the same covariates: recipient age (quadratic) and donor age (quadratic), donor type (living or deceased; for the total cohort only), cold ischemia time (for donation after brain death [DBD] and donation after cardiac death [DCD]), time on dialysis in years (quadratic) and induction therapy with interleukin‐2 receptor blocker [Color figure can be viewed at http://www.wileyonlinelibrary.com]