Bortezomib in the treatment of antibody‐mediated rejection in pediatric kidney transplant recipients: A multicenter Midwest Pediatric Nephrology Consortium study

• Published in: Pediatric transplantation 2017-05, Vol.21 (3), p.np-n/a
• Main Authors: Kizilbash, Sarah, Claes, Donna, Ashoor, Isa, Chen, Ashton, Jandeska, Sara, Matar, Raed Bou, Misurac, Jason, Sherbotie, Joseph, Twombley, Katherine, Verghese, Priya
• Format: Article
• Language: English
• Subjects: Adolescent; Antibodies - immunology; antibody‐mediated rejection; Biopsy; Bortezomib; Bortezomib - therapeutic use; Child; Child, Preschool; Consortia; Female; Glomerular Filtration Rate; Graft rejection; Graft Rejection - immunology; Humans; Immune System; Immunoglobulins, Intravenous - therapeutic use; Infant; Inhibitor drugs; Intravenous administration; Kaplan-Meier Estimate; Kidney Transplantation; Kidney transplants; Liver; Male; Midwestern United States; Monoclonal antibodies; Nephrology; pediatric kidney transplant; Pediatrics; Plasmapheresis; Retrospective Studies; Rituximab; Rituximab - therapeutic use; Side effects; Transplantation; Transplants & implants; Treatment Outcome; Young Adult
• ISSN: 1397-3142; 1399-3046
• DOI: 10.1111/petr.12873

Antibody‐mediated rejection leads to allograft loss after kidney transplantation. Bortezomib has been used in adults for the reversal of antibody‐mediated rejection; however, pediatric data are limited. This retrospective study was conducted in collaboration with the Midwest Pediatric Nephrology Consortium. Pediatric kidney transplant recipients who received bortezomib for biopsy‐proven antibody‐mediated rejection between 2008 and 2015 were included. The objective was to characterize the use of bortezomib in pediatric kidney transplant recipients. Thirty‐three patients received bortezomib for antibody‐mediated rejection at nine pediatric kidney transplant centers. Ninety percent of patients received intravenous immunoglobulin, 78% received plasmapheresis, and 78% received rituximab. After a median follow‐up of 15 months, 65% of patients had a functioning graft. The estimated glomerular filtration rate improved or stabilized in 61% and 36% of patients at 3 and 12 months post‐bortezomib, respectively. The estimated glomerular filtration rate at diagnosis significantly predicted estimated glomerular filtration rate at 12 months after adjusting for chronic histologic changes (P .001). Fifty‐six percent of patients showed an at least 25% reduction in the mean fluorescence intensity of the immune‐dominant donor‐specific antibody, 1‐3 months after the first dose of bortezomib. Non‐life‐threatening side effects were documented in 21 of 33 patients. Pediatric kidney transplant recipients tolerated bortezomib without life‐threatening side effects. Bortezomib may stabilize estimated glomerular filtration rate for 3‐6 months in pediatric kidney transplant recipients with antibody‐mediated rejection.