title: Bortezomib-based treatment of acute antibody-mediated rejection: a case report.
abstract: Antibody-mediated rejection (AMR) is an important factor affecting survival after renal transplantation. A highly selective proteasome inhibitor, bortezomib, clears activated plasma cells from the body and has important therapeutic effect on AMR. We investigated the effects of bortezomib on AMR in a patient after a second renal transplant. Biopsy confirmed the diagnosis of mixed cellular rejection and AMR. Bortezomib was administered on day 1 (1.3 mg/m(2)), day 4 (1.0 mg/m(2)), and day 8 (1.0 mg/m(2)). On the same days, 250 mg methylprednisolone was administered once, and cyclosporine dose (5 mg·kg(-1)·day(-1)) was reduced by 50%. Oral mycophenolate mofetil and steroid were withdrawn on day 1 of bortezomib treatment. Intermittent double-filtration plasmapheresis was also performed. We monitored parameters, including T lymphocyte subsets, CD139 and CD19 expression, panel reactive antibody (PRA), and serum creatinine concentration. At follow-up 6 months after bortezomib treatment, we observed: 1) serum creatinine stabilized at 130 μM from a peak level of 337 μM; 2) PRA decreased from a maximum of 66.7 to 0%; 3) blood plasma cell percentage rebounded after significantly decreasing following the first dose of bortezomib; 4) in renal allograft biopsy, immunohistochemical staining for C4d shifted from strongly positive to negative, and cellular rejection shifted from type IIA to borderline; and 5) adverse effects such as platelet suppression, hypotension, and grade 3 peripheral neuropathy emerged. Bortezomib effectively treated antibody-mediated renal transplantation rejection in this case study, but clinical trials with large sample sizes are still needed to explore clinical safety and tolerability.
authors.affiliation: Department of Urology, General Hospital of Chinese PLA, Beijing, China.|Organ Transplant Research Institute, the 309th Hospital of Chinese PLA, Beijing, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Cadre Ward, the 309th Hospital of Chinese PLA, Beijing, China.
authors.forename: X L
authors.initials: XL
authors.lastname: Li
authors.affiliation: Organ Transplant Research Institute, the 309th Hospital of Chinese PLA, Beijing, China.
authors.forename: X G
authors.initials: XG
authors.lastname: Xu
authors.affiliation: Organ Transplant Research Institute, the 309th Hospital of Chinese PLA, Beijing, China.
authors.forename: B Y
authors.initials: BY
authors.lastname: Shi
authors.affiliation: Organ Transplant Research Institute, the 309th Hospital of Chinese PLA, Beijing, China.
authors.forename: Z M
authors.initials: ZM
authors.lastname: Zhang
authors.affiliation: Organ Transplant Research Institute, the 309th Hospital of Chinese PLA, Beijing, China.
authors.forename: Z L
authors.initials: ZL
authors.lastname: Li
authors.affiliation: Organ Transplant Research Institute, the 309th Hospital of Chinese PLA, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Han
authors.affiliation: Organ Transplant Research Institute, the 309th Hospital of Chinese PLA, Beijing, China.
authors.forename: W Q
authors.initials: WQ
authors.lastname: Zhou
authors.affiliation: Organ Transplant Research Institute, the 309th Hospital of Chinese PLA, Beijing, China.
authors.forename: C Q
authors.initials: CQ
authors.lastname: Chen
authors.affiliation: Organ Transplant Research Institute, the 309th Hospital of Chinese PLA, Beijing, China.
authors.forename: M
authors.initials: M
authors.lastname: Cai
authors.affiliation: Department of Urology, General Hospital of Chinese PLA, Beijing, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000906:Antibodies / Q000009:adverse effects* / Q000276:immunology; D000069286:Bortezomib / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016030:Kidney Transplantation / Q000009:adverse effects*; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D014184:Transplantation, Homologous / Q000009:adverse effects
chemical_list: D000906:Antibodies; D000069286:Bortezomib; D009173:Mycophenolic Acid