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Treatment of acute antibody‐mediated rejection using bortezomib: a case report

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/m2) 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.