title: Treatment of antibody-mediated rejection in kidney transplant recipients: a single-center experience with a bortezomib-based regimen.
abstract: OBJECTIVE
  Antibody-mediated rejection after kidney transplant is less responsive to conventional antirejection therapies. The proteasome inhibitor bortezomib has activity against mature plasma cells that produce damaging donor-specific antibodies. We present our experience of using a bortezomib-based regimen in patients with severe antibody-mediated rejection.
  
  
  METHODS
  A retrospective chart review was performed on patients with biopsy-proven antibody-mediated rejection after kidney transplant at our institution over 12 months. Diagnosis of antibody-mediated rejection was made on the basis of positive peritubular capillary C4d staining along with either histologic evidence of acute rejection or positive donor-specific antibody titers. Treatment for antibody-mediated rejection included plasmapheresis, intravenous immunoglobulin, steroids, single-dose rituximab (375 mg/m²) along with bortezomib (1.3 mg/m²) on days 1, 4, 8, and 11. Antibody-mediated rejection was diagnosed in 6 patients. Patients received induction with either alemtuzumab (n=4) or rabbit-antithymocyte globulin (n=2) and were maintained on a tacrolimus/mycophenolate mofetil/early steroid withdrawal protocol.
  
  
  RESULTS
  Four of 6 patients responded to treatment. Patients had stable kidney function during followup (median 14 months) after bortezomib therapy.
  
  
  CONCLUSIONS
  In this series, we demonstrated the effectiveness of a bortezomib-based treatment regimen in achieving reduction of donor-specific antibody titers and stable renal function in patients experiencing severe antibody-mediated rejection.
authors.affiliation: Division of Nephrology and Hypertension, Allegheny General Hospital, Pittsburgh, PA 15212, USA.
authors.forename: Janice G
authors.initials: JG
authors.lastname: Nigos
authors.forename: Swati
authors.initials: S
authors.lastname: Arora
authors.forename: Parineesha
authors.initials: P
authors.lastname: Nath
authors.forename: Sabiha M
authors.initials: SM
authors.lastname: Hussain
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Marcus
authors.forename: Tina Y
authors.initials: TY
authors.lastname: Ko
authors.forename: Kalathil K
authors.initials: KK
authors.lastname: Sureshkumar
mesh_terms: D000328:Adult; D000906:Antibodies / Q000276:immunology; D001897:Boronic Acids / Q000008:administration & dosage*; D000069286:Bortezomib; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D010950:Plasma Cells / Q000276:immunology; D061988:Proteasome Inhibitors / Q000008:administration & dosage*; D011719:Pyrazines / Q000008:administration & dosage*; D012189:Retrospective Studies; D014019:Tissue Donors
chemical_list: D000906:Antibodies; D001897:Boronic Acids; D061988:Proteasome Inhibitors; D011719:Pyrazines; D000069286:Bortezomib