title: Treatment of acute antibody-mediated rejection using bortezomib: a case report.
abstract: Here we report the successful treatment of acute antibody-mediated rejection (AMR) with bortezomib. Bortezomib rescue treatment was administered after a 42-year-old woman failed to respond to steroid pulse and plasmapheresis with intravenous immunoglobulin (IVIG). The patient underwent a second renal transplantation with a deceased donor kidney. She was treated pre-operatively with rituximab (200 mg/body) and underwent plasmapheresis twice (day-1 and operation day) because ELISA screening revealed that her pre-operative peak panel reactive antibody (PRA) composition was 100% class I and 100% class II and 15 times of cross-match positive history during the waiting period for transplantation. The patients received induction therapy with Simulect (an IL-2-blocking agent). A 1-hour protocol biopsy revealed C4d-positivity and mild peritubular capillary inflammation. This was suggestive of early AMR-associated changes. After transplantation, the patient underwent plasmaphereses (nine times) with low-dose IVIG (2 mg/kg). Despite this treatment regimen, serum creatinine levels increased to 3.4 mg/dL on post-transplant day 15. A second graft biopsy was performed, which showed overt AMR with glomerulitis, peritubular capillary inflammation and no C4d deposition. On post-operative day (POD) 22, treatment with four doses of bortezomib (1.3 mg/m(2) ) was initiated with the patient's consent. On POD 55, renal function had recovered and serum creatinine was 1.5 mg/dL. In summary, bortezomib was administered as a rescue treatment for a patient who developed AMR that was refractory to a combination of plasmaphereses with low-dose IVIG and preemptive administration of rituximab.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Bong Seng Hospital, Busan, Korea.
authors.forename: Yong-Hun
authors.initials: YH
authors.lastname: Sin
authors.affiliation: Department of Pathology, Yeungnam University College of Medicine, Daegu, Korea.
authors.forename: Yong-Jin
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Bong Seng Hospital, Busan, Korea.
authors.forename: Joon Seok
authors.initials: JS
authors.lastname: Oh
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Bong Seng Hospital, Busan, Korea.
authors.forename: Jin Ho
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Bong Seng Hospital, Busan, Korea.
authors.forename: Seong Min
authors.initials: SM
authors.lastname: Kim
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Bong Seng Hospital, Busan, Korea.
authors.forename: Joong Kyung
authors.initials: JK
authors.lastname: Kim
mesh_terms: D000208:Acute Disease; D000328:Adult; D064591:Allografts; D001706:Biopsy; D000069286:Bortezomib / Q000627:therapeutic use*; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006801:Humans; D056724:Immunity, Humoral / Q000187:drug effects*; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D016030:Kidney Transplantation / Q000009:adverse effects*; D012086:Reoperation; D016879:Salvage Therapy; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D000069286:Bortezomib
keywords: Bortezomib; acute antibody mediated rejection; refractory antibody mediated rejection; repeated allograft biopsy