title: Bortezomib in the treatment of antibody-mediated rejection in pediatric kidney transplant recipients: A multicenter Midwest Pediatric Nephrology Consortium study.
abstract: 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.
authors.affiliation: University of Minnesota, Minneapolis, MN, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kizilbash
authors.affiliation: Cincinnati Children's Hospital, Cincinnati, OH, USA.
authors.forename: Donna
authors.initials: D
authors.lastname: Claes
authors.affiliation: Children's Hospital New Orleans, New Orleans, LA, USA.
authors.forename: Isa
authors.initials: I
authors.lastname: Ashoor
authors.affiliation: Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Ashton
authors.initials: A
authors.lastname: Chen
authors.affiliation: Rush University, Chicago, IL, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Jandeska
authors.affiliation: Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Raed Bou
authors.initials: RB
authors.lastname: Matar
authors.affiliation: University of Iowa, Iowa, IA, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Misurac
authors.affiliation: University of Utah, Salt Lake City, UT, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Sherbotie
authors.affiliation: Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Twombley
authors.affiliation: University of Minnesota, Minneapolis, MN, USA.
authors.forename: Priya
authors.initials: P
authors.lastname: Verghese
mesh_terms: D000293:Adolescent; D000906:Antibodies / Q000276:immunology*; D001706:Biopsy; D000069286:Bortezomib / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D007107:Immune System; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007223:Infant; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation; D008297:Male; D015146:Midwestern United States; D012189:Retrospective Studies; D000069283:Rituximab / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000906:Antibodies; D016756:Immunoglobulins, Intravenous; D000069283:Rituximab; D000069286:Bortezomib
keywords: antibody-mediated rejection; bortezomib; pediatric kidney transplant