Background: Desensitization (DSZ) strategies have been developed in kidney transplantation recently. The aim of this study is to investigate the usefulness of bortezomib based DSZ (BZB-DSZ) therapy in highly sensitized living and deceased donor kidney transplantation.
Methods: We applied this BZB-DSZ protocol to 20 patients of 14 living donor kidney transplantation (LDKT) candidates with positive T-CDC (complement dependent cytotoxicity) crossmatch at baseline or refractory to DSZ using rituximab and plasmapheresis (RTX/PP) and of six deceased donor kidney transplantation (DDKT) candidates, when (1) waiting time 10 years, (2) panel reactive antibody values 50%, and (3) previous history of a positive T cell crossmatch with potential deceased donor between July 2012 and Nov 2022 in our center.
Results: Clinical outcomes revealed 16 of 20 patients (80%) underwent BZB-DSZ proceeded with transplantation successfully, one refused the transplant, and three are still awaiting for DDKT. Among LDKT candidates, 8 of 10 candidates (80%) with a positive T-CDC turned negative. Mostly the mean fluorescence intensity (MFI) level of donor-specific anti-human leukocyte antigen (HLA) antibody (HLA-DSA) markedly decreased to target level (MFI<5,000) except for those patients who were refractory to RTX/PP based DSZ with marginal decease of MFI. Among DDKT candidates, the count of strong HLA-DSA (MFI>10,000) decreased after DSZ. Out of them, three showed negative T cell crossmatch test to deceased donor as they could proceed with DDKT. All 16 patients who proceeded KT did not show hyper-acute rejection but eight cases (50%) showed biopsy-proven allograft rejection, with an antibody-mediated rejection rate of 87.5%. Death censored allograft survival during median follow-up duration of 35 months was 93.75%. Three received antiviral treatment for cytomegalovirus viremia, and one of them expired due to pneumonia sepsis.
Conclusions: BZB-DSZ is effective to reduce HLA-DSA and enables highly sensitized patients to take kidney transplantation, and showed acceptable allograft outcomes.