Proteasome inhibition with bortezomib: an effective therapy for severe antibody mediated rejection after renal transplantation

• Published in: Clinical nephrology Vol. 77; no. 3; p. 246
• Main Authors: Sureshkumar, Kalathil K, Hussain, Sabiha M, Marcus, Richard J, Ko, Tina Y, Khan, Akhtar S, Tom, Kusum, Vivas, Carlos A, Parris, George, Jasnosz, Katherine M, Thai, Ngoc L
• Format: Journal Article
• Language: English
• Published: Germany 01-03-2012
• Subjects: Adult; Biopsy; Boronic Acids - therapeutic use; Bortezomib; Female; Graft Rejection - drug therapy; Graft Rejection - enzymology; Graft Rejection - immunology; Graft Rejection - pathology; Humans; Isoantibodies - blood; Kidney Failure, Chronic - surgery; Kidney Transplantation - immunology; Male; Middle Aged; Protease Inhibitors - therapeutic use; Proteasome Endopeptidase Complex - metabolism; Proteasome Inhibitors; Pyrazines - therapeutic use; Severity of Illness Index; Treatment Outcome
• ISSN: 0301-0430
• DOI: 10.5414/CN107156

Antibody-mediated rejection (AMR) following renal transplantation is less responsive to conventional anti-rejection therapies. Plasmapheresis (PP), intravenous immunoglobulin (IVIg), rabbit antithymocyte globulin (rATG) and rituximab deplete immature B-cells but not mature plasma cells. The proteasome inhibitor bortezomib has activity against mature plasma cell, the source of damaging donor-specific antibody (DSA).We present the successful use of bortezomib in 2 patients who developed AMR following kidney transplantation. The first patient was a 54-year-old white female who received living-unrelated kidney transplantation from her husband. She developed severe AMR early after transplantation with rising DSA titers consistent with an anamnestic immune response by memory cells to the donor antigens. Renal function deteriorated despite treatment with pulse methylprednisolone (MP), PP and IVIg. After initiation of therapy with bortezomib, DSA titers became negative and serum creatinine returned to baseline with histological resolution of AMR. The second patient was a 19-year-old white male who received deceased donor kidney transplantation and developed AMR within 2 weeks, refractory to therapy with pulse MP, PP and IVIg with rising DSA. Bortezomib use resulted in disappearance of DSA and renal function improvement. Both patients tolerated the treatment well with stable renal function at last follow-up. The novel mechanisms of action and preliminary results with bortezomib are encouraging, but require larger studies and longer follow-up.