Prolonged immunosuppression preserves nonsensitization status after kidney transplant failure

Abstract

Background: When kidney transplants fail, transplant medications are discontinued to reduce immunosuppression-related risks. However, retransplant candidates are at risk for allosensitization which prolonging immunosuppression may minimize. We hypothesized that for these patients, a prolonged immunosuppression withdrawal after graft failure preserves nonsensitization status (PRA 0%) better than early immunosuppression withdrawal.

Methods: We retrospectively examined subjects transplanted at a single center between July 1, 1999 and December 1, 2009 with a non-death-related graft loss. Subjects were stratified by timing of immunosuppression withdrawal after graft loss: early (≤3 months) or prolonged (>3 months). Retransplant candidates were eligible for the main study where the primary outcome was nonsensitization at retransplant evaluation. Non-retransplant candidates were included in the safety analysis only.

Results: We found 102 subjects with non-death-related graft loss of which 49 were eligible for the main study. Nonsensitization rates at retransplant evaluation were 30% and 66% for the early and prolonged immunosuppression withdrawal groups, respectively (P=0.01). After adjusting for cofactors such as blood transfusion and allograft nephrectomy, prolonged immunosuppression withdrawal remained significantly associated with nonsensitization (adjusted odds ratio=5.78, 95% CI [1.37-24.44]). No adverse safety signals were seen in the prolonged immunosuppression withdrawal group compared to the early immunosuppression withdrawal group.

Conclusions: These results suggest that prolonged immunosuppression may be a safe strategy to minimize sensitization in retransplant candidates and provide the basis for larger or prospective studies for further verification.

Figure 1. Subject Selection

IS = immunosuppression.

Figure 2. Nonsensitization Stratified by Immunosuppression Withdrawal Duration after Graft Failure

IS = immunosuppression.

Figure 3. Multivariate Analysis of Nonsensitization after Graft Failure, N=49

IS = immunosuppression. LDA = lymphocyte depleting antibody.

Figure 4. Mean Panel Reactive Antibody Stratified by Immunosuppression Withdrawal Duration after Graft Failure

Eleven subjects were excluded from this analysis due to discordant PRA detection techniques prior to graft placement and after graft failure. IS = immunosuppression. PRA = panel reactive antibody.