[PubMed] [Google Scholar] 33. 30% and 66% for the PX-866 (Sonolisib) 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% C.I. [1.37-24.44]). No adverse safety signals PX-866 (Sonolisib) 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. strong class=”kwd-title” Keywords: kidney, transplantation, sensitization, immunosuppression withdrawal INTRODUCTION Kidney transplantation is usually life-sparing for patients with end stage renal disease (ESRD) who are on the waitlist (1-3). Projected patient lifetime almost doubles after deceased donor kidney transplantation compared with remaining around the waitlist (4). However when a kidney transplant fails, the survival benefit is lost (5,6). Additionally, more sepsis and infection-related deaths have been reported after transplant failure compared to patients who retain transplant function (5,7). Yet, patients who are retransplanted benefit from a reduction in mortality when compared with their wait-listed counterparts with prior transplant failure (8). A growing number of patients with a failed kidney transplant are relisted for a subsequent transplant. United States registry data show that approximately 20% of all ESRD patients around the kidney transplant waiting list have a prior failed transplant (9). However, retransplanting these patients is challenging because prior transplantation is usually a risk factor for human leukocyte antigen (HLA) sensitization which may limit compatible organs and prolong waitlist occasions (10,11). Furthermore, kidney transplant failure itself carries a high risk of sensitization which is probably Mouse monoclonal to Influenza A virus Nucleoprotein related to several factors like transplant nephrectomy, blood transfusion, and sudden immunosuppression cessation (12-15). When kidney transplants fail, transplant medications are commonly stopped to reduce the risks associated with immunosuppression, namely contamination and premature death (16,17). However, when to withdraw immunosuppression remains an unanswered question. Potential benefits of prolonged immunosuppression withdrawal include a reduction in graft rejection and preservation of residual renal function (18,19), but another more intriguing benefit may be minimizing the risk of sensitization after transplant failure (15). By minimizing sensitization risk, patients may have a greater opportunity to receive a subsequent life-sparing kidney transplant. We hypothesized that in patients referred for retransplantation, prolonged immunosuppression withdrawal after kidney transplant failure reduces the risk of sensitization and better preserves their nonsensitization status compared to early immunosuppression withdrawal. In addition, we evaluated whether prolonged immunosuppression withdrawal was associated with additional safety risks compared to early withdrawal. RESULTS Out of 1448 subjects who received a kidney transplant between 7/1/1999-12/1/2009, 102 subjects were identified with a non-death related graft failure. Forty-nine subjects were evaluated for kidney retransplantation (main study group). Of the main study participants, 20 and 29 subjects had their immunosuppression withdrawn at 3 months (early) and 3 months (prolonged) respectively (Physique 1). The main study group baseline characteristics were comparable in both withdrawal groups (Table 1). The median durations for immunosuppression after graft failure were 24 days [25%,75% Quartiles: 16, 41 days] and 357 days [25%,75% Quartiles: 210, 595 days] for the early and prolonged withdrawal groups respectively. Prolonged immunosuppression after graft failure was seen in 5 subjects with a functioning non-renal solid organ transplant. Rates of antibody mediated rejection were similar and no subject received a prolonged treatment lasting 7 days. To salvage graft function, no differences were seen in the use of depleting antibody (4 v. 5 subjects), IVIG (2 v. 0 subjects), or plasmapheresis (1 v. 0 subjects) between the early and prolonged withdrawal groups respectively. A third of grafts failed within a 12 months of transplantationlargely due to primary nonfunction, thrombosis, or acute rejectionwhich resulted in a low median graft survival. Open in a separate window Physique 1 Subject SelectionIS = immunosuppression. Table 1 Baseline Subject Characteristics thead th rowspan=”2″ align=”left” valign=”top” colspan=”1″ Baseline Characteristics /th th colspan=”3″ align=”center” valign=”top” rowspan=”1″ Main Study Group N=49 /th th colspan=”3″ align=”center” valign=”top” rowspan=”1″ All Subjects N=102 /th th align=”center” valign=”top” rowspan=”1″ colspan=”1″ Is usually Withdrawal 3 months N=20 /th th align=”center” PX-866 (Sonolisib) valign=”top” rowspan=”1″ colspan=”1″ Is usually Withdrawal 3 months N=29 /th th align=”center” valign=”top” rowspan=”1″ colspan=”1″ P Value /th th align=”center” valign=”top” rowspan=”1″ colspan=”1″ Is usually Withdrawal 3 months N=52 /th th align=”center” valign=”top” rowspan=”1″ colspan=”1″ Is usually Withdrawal 3 months N=50 /th th align=”center” valign=”top” rowspan=”1″ colspan=”1″ P Value /th /thead PX-866 (Sonolisib) Age at Graft Failure, Years, Mean SD43 1243 150.926249 1446 140.2818Female Gender, N (%)11 (55)9 (31)0.093421 (41)18 (38)0.7083Prior Pregnancy,.