Treatment of antibody-mediated rejection in kidney transplant recipients: a single-center experience with a bortezomib-based regimen

• Published in: Experimental and clinical transplantation Vol. 10; no. 6; pp. 609 - 613
• Main Authors: Nigos, Janice G, Arora, Swati, Nath, Parineesha, Hussain, Sabiha M, Marcus, Richard J, Ko, Tina Y, Sureshkumar, Kalathil K
• Format: Journal Article
• Language: English
• Published: Turkey 01-12-2012
• Subjects: Adult; Antibodies - immunology; Boronic Acids - administration & dosage; Bortezomib; Graft Rejection - immunology; Humans; Kidney Transplantation; Male; Plasma Cells - immunology; Proteasome Inhibitors - administration & dosage; Pyrazines - administration & dosage; Retrospective Studies; Tissue Donors
• ISSN: 1304-0855; 2146-8427
• DOI: 10.6002/ect.2012.0131

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.
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.
Four of 6 patients responded to treatment. Patients had stable kidney function during followup (median 14 months) after bortezomib therapy.
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.