title: Bortezomib may stabilize pediatric renal transplant recipients with antibody-mediated rejection.
abstract: Current therapeutic strategies to effectively treat antibody-mediated rejection (AMR) are insufficient. Thus, we aimed to determine the benefit of a therapeutic protocol using bortezomib for refractory C4d + AMR in pediatric kidney transplant patients.
  
  
  
  We examined seven patients with treatment-refractory C4d + AMR. Immunosuppression included antithymocyte globulin or anti-CD25 monoclonal antibody for induction therapy with maintenance corticosteroids, calcineurin inhibitor, and anti-metabolite. Estimated glomerular filtration rate (eGFR) calculated by the Schwartz equation, biopsy findings assessed by 2013 Banff criteria, and human leukocyte antigen (HLA) donor-specific antibodies (DSA) performed using the Luminex single antigen bead assay were monitored pre- and post- bortezomib therapy.
  
  
  
  Seven patients (86 % male, 86 % with ≥6/8 HLA mismatch, and 14 % with pre-formed DSA) age 5 to 19 (median 15) years developed refractory C4d + AMR between 1 and 145 (median 65) months post-transplantation. All patients tolerated bortezomib. One patient had allograft loss. Of the six patients with surviving grafts (86 %), mean pre-bortezomib eGFR was 42 ml/min/1.73 m(2) and the mean 1 year post-bortezomib eGFR was 53 ml/min/1.73 m(2). Five of seven (71 %) had improvement of histological findings of AMR, C4d staining, and/or acute cellular rejection. Reduction in HLA DSAs was more effective for class I than class II.
  
  
  
  Bortezomib appears safe and may correlate with stabilization of eGFR in pediatric kidney transplant patients with refractory C4d + AMR.
authors.affiliation: Department of Pediatrics, Division of Nephrology, David Geffen School of Medicine at UCLA, University of California Los Angeles, PO Box 951752, Los Angeles, CA, 90095, USA. mpearl@mednet.ucla.edu.
authors.forename: Meghan H
authors.initials: MH
authors.lastname: Pearl
authors.affiliation: Department of Pediatrics, Division of Nephrology, David Geffen School of Medicine at UCLA, University of California Los Angeles, PO Box 951752, Los Angeles, CA, 90095, USA.
authors.forename: Anjali B
authors.initials: AB
authors.lastname: Nayak
authors.affiliation: Department of Pediatrics, Division of Nephrology, David Geffen School of Medicine at UCLA, University of California Los Angeles, PO Box 951752, Los Angeles, CA, 90095, USA.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Ettenger
authors.affiliation: Pediatric Nephrology and Transplant Immunology, Cedars Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Dechu
authors.initials: D
authors.lastname: Puliyanda
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, PO Box 951752, Los Angeles, CA, USA.
authors.forename: Miguel Fernando
authors.initials: MF
authors.lastname: Palma Diaz
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, PO Box 951752, Los Angeles, CA, USA.
authors.forename: Qiuheng
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, PO Box 951752, Los Angeles, CA, USA.
authors.forename: Elaine F
authors.initials: EF
authors.lastname: Reed
authors.affiliation: Department of Pediatrics, Division of Nephrology, David Geffen School of Medicine at UCLA, University of California Los Angeles, PO Box 951752, Los Angeles, CA, 90095, USA.
authors.forename: Eileen W
authors.initials: EW
authors.lastname: Tsai
mesh_terms: D000293:Adolescent; D000069286:Bortezomib / Q000627:therapeutic use*; D002675:Child, Preschool; D015935:Complement C4b / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy*; D006085:Graft Survival / Q000187:drug effects; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D010446:Peptide Fragments / Q000276:immunology; D061988:Proteasome Inhibitors / Q000627:therapeutic use*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D010446:Peptide Fragments; D061988:Proteasome Inhibitors; D000069286:Bortezomib; D015935:Complement C4b; C032261:complement C4d
keywords: Antibody-mediated rejection; Bortezomib; Kidney; Non-adherence; Pediatric; Proteasome inhibitor; Transplant