Pediatric Transplantaton 2017; e12873; wileyonlinelibrary.com/journal/petr | 1 of 8 DOI: 10.1111/petr.12873 © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Accepted: 18 November 2016 DOI: 10.1111/petr.12873 ORIGINAL ARTICLE Bortezomib in the treatment of antbody-mediated rejecton in pediatric kidney transplant recipients: A multcenter Midwest Pediatric Nephrology Consortum study Sarah Kizilbash 1 | Donna Claes 2 | Isa Ashoor 3 | Ashton Chen 4 | Sara Jandeska 5 | Raed Bou Matar 6 | Jason Misurac 7 | Joseph Sherbote 8 | Katherine Twombley 9 | Priya Verghese 1 1 University of Minnesota, Minneapolis, MN, USA 2 Cincinnat Children’s Hospital, Cincinnat, OH, USA 3 Children’s Hospital New Orleans, New Orleans, LA, USA 4 Wake Forest School of Medicine, Winston- Salem, NC, USA 5 Rush University, Chicago, IL, USA 6 Cleveland Clinic, Cleveland, OH, USA 7 University of Iowa, Iowa, IA, USA 8 University of Utah, Salt Lake City, UT, USA 9 Medical University of South Carolina, Charleston, SC, USA Correspondence Sarah Kizilbash, University of Minnesota, Minneapolis, MN, USA. Email: kizil010@umn.edu Abstract Antbody-mediated rejecton leads to allograf loss afer kidney transplantaton. Bortezomib has been used in adults for the reversal of antbody-mediated rejecton; however, pediatric data are limited. This retrospectve study was conducted in collabora- ton with the Midwest Pediatric Nephrology Consortum. Pediatric kidney transplant re- cipients who received bortezomib for biopsy-proven antbody-mediated rejecton between 2008 and 2015 were included. The objectve was to characterize the use of bortezomib in pediatric kidney transplant recipients. Thirty-three patents received bort- ezomib for antbody-mediated rejecton at nine pediatric kidney transplant centers. Ninety percent of patents received intravenous immunoglobulin, 78% received plasma- pheresis, and 78% received rituximab. Afer a median follow-up of 15 months, 65% of patents had a functoning graf. The estmated glomerular fltraton rate improved or stabilized in 61% and 36% of patents at 3 and 12 months post-bortezomib, respectvely. The estmated glomerular fltraton rate at diagnosis signifcantly predicted estmated glo- merular fltraton rate at 12 months afer adjustng for chronic histologic changes (P .001). Fify-six percent of patents showed an at least 25% reducton in the mean fuorescence intensity of the immune-dominant donor-specifc antbody, 1-3 months afer the frst dose of bortezomib. Non-life-threatening side efects were documented in 21 of 33 pa- tents. Pediatric kidney transplant recipients tolerated bortezomib without life-threatening side efects. Bortezomib may stabilize estmated glomerular fltraton rate for 3-6 months in pediatric kidney transplant recipients with antbody-mediated rejecton. KEYWORDS antbody-mediated rejecton, bortezomib, pediatric kidney transplant 1 | INTRODUCTION The current KDIGO recommendatons for the treatment of antbody- mediated rejecton include plasma exchange, intravenous immunoglobulin, ant-CD20 antbody, and lymphocyte-depletng antbody with or without steroids. 1 However, there is litle evidence supportng the use of these agents and the demonstrated beneft is inconsistent. 2 It has been postu- lated that the limited efcacy of the current therapies is due to plasma cell sparing, the primary source of the ofending donor-specifc antbodies. Bortezomib is a proteasome inhibitor, which is commonly used for the treatment of plasma cell dyscrasias. 3 Bortezomib selectvely Abbreviatons: AMR, antbody-mediated rejecton; DSA, donor-specifc antbodies; eGFR, estmated glomerular fltraton rate; HLA, human leukocyte antgen; MFI, mean fuorescence intensity; MHC, major histocompatbility complex; PKtx, pediatric kidney transplant; PRA, panel reactve antbody tters.