The Effect of Bortezomib on Antibody-Mediated Rejection after Kidney Transplantation

• Published in: Yonsei medical journal Vol. 56; no. 6; pp. 1638 - 1642
• Main Authors: Lee, Juhan, Kim, Beom Seok, Park, Yongjung, Lee, Jae Geun, Lim, Beom Jin, Jeong, Hyeon Joo, Kim, Yu Seun, Huh, Kyu Ha
• Format: Journal Article
• Language: English
• Published: Korea (South) Yonsei University College of Medicine 01.11.2015; 연세대학교의과대학
• Subjects: Adolescent; Adult; Antibodies, Monoclonal - therapeutic use; Antineoplastic Agents - therapeutic use; Boronic Acids - therapeutic use; Bortezomib - therapeutic use; Female; Graft Rejection - drug therapy; Graft Rejection - prevention & control; Humans; Immunoglobulins, Intravenous - therapeutic use; Immunologic Factors - therapeutic use; Isoantibodies; Kidney Failure, Chronic - surgery; Kidney Transplantation; Male; Middle Aged; Original; Plasmapheresis; Pyrazines - administration & dosage; Transplantation, Homologous; 의학일반; bortezomib; HLA antibodies; Angiotensin II type 1 receptor antibodies; kidney transplantation; antibody-mediated rejection
• ISSN: 0513-5796; 1976-2437
• DOI: 10.3349/ymj.2015.56.6.1638

Recently, bortezomib has been used to treat antibody-mediated rejection (AMR) refractory to conventional treatment such as plasmapheresis, intravenous immunoglobulin, and rituximab. The authors aimed to describe their experiences when bortezomib was used to treat refractory AMR. Eleven refractory AMR episodes treated with bortezomib were included in this study. The patients received one or two cycles of bortezomib (1.3 mg/m²) on days 1, 4, 8, and 11. Bortezomib effectively reduced antibodies against various targets, including human leukocyte antigen (HLA) class I and II, ABO blood group antigen, and angiotensin II type 1 receptor. Antibodies were depleted or reduced significantly in eight AMR episodes. Overall, there was a significant improvement in the mean estimated glomerular filtration rate (eGFR) at 3 months after therapy (36.91±22.15 mL/min/1.73 m²) versus eGFR at time of AMR diagnosis (17.00±9.25 mL/min/1.73 m²; p=0.007). All six early-onset AMR episodes (within 6 months post-transplantation) showed full recovery of allograft function. Additionally, three of the five late-onset AMR episodes (>6 months post-transplantation) showed improved allograft function. Anti-humoral treatment based on bortezomib might be an effective strategy against refractory AMR caused by various types of antibodies. Notably, this treatment could be more effective in early-onset AMR than in late-onset AMR.