Therapeutic dosingtiming and efficacy of bortezomib for antibody-mediated kidney transplant rejection

Abstract

Objective To explore whether therapeutic dosing timing of proteasome inhibitor bortezomib(BZ) would impact its clinical efficacy. Methods From 2012 to 2018, 35 biopsy-confirmed cases of acute antibody-mediated kidney transplant rejection (AMR) were collected. They received intravenous immunoglobulin (IVIG) plus sirolimus (Sir) plus bortezomib (BZ). Three groups were assigned according to dosing timing of BZ. After a diagnosis of AMR, ET (early treatment) group began BZ dosing within 7 days (n=16) while DT (delayed treatment) group within 8-14 days (n=11) and LT (late treatment) group >14 days (n=8). Their clinical parameters and incidence of complications were analyzed. Results DSA reversal rate of ET, DT and LT groups was 87.5%, 45.5% and 25.0% (P=0.006) while DSA declining rate 93.8%, 90.9% and 50% respectively (P=0.019); recurrent rate of AMR was lower in ET/DT group than LT group (6.6% vs 10% vs 75%, P=0.042). No significant differences existed in blood perfusion score of allograft at 1 month post-dosing among three groups. In three groups, creatinine (Cr) of ET group was lower than DT group at month 1/3/12 while DT group was lower than LT group. No significant difference existed in the incidence of adverse reactions among 3 groups. Conclusions More likely to enter the window period, early dosing of BZ is more effective for treating acute AMR. An earlier intervention yields a better efficacy. Key words: Kidney transplantation; DSA; Rejection; Bortezomib