PMID- 27048228
OWN - NLM
STAT- MEDLINE
DCOM- 20170918
LR  - 20220408
IS  - 1432-198X (Electronic)
IS  - 0931-041X (Print)
IS  - 0931-041X (Linking)
VI  - 31
IP  - 8
DP  - 2016 Aug
TI  - Bortezomib may stabilize pediatric renal transplant recipients with 
      antibody-mediated rejection.
PG  - 1341-8
LID - 10.1007/s00467-016-3319-3 [doi]
AB  - BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 
      Bortezomib appears safe and may correlate with stabilization of eGFR in pediatric 
      kidney transplant patients with refractory C4d + AMR.
FAU - Pearl, Meghan H
AU  - Pearl MH
AD  - 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.
FAU - Nayak, Anjali B
AU  - Nayak AB
AD  - 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.
FAU - Ettenger, Robert B
AU  - Ettenger RB
AD  - 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.
FAU - Puliyanda, Dechu
AU  - Puliyanda D
AD  - Pediatric Nephrology and Transplant Immunology, Cedars Sinai Medical Center, Los 
      Angeles, CA, USA.
FAU - Palma Diaz, Miguel Fernando
AU  - Palma Diaz MF
AD  - Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, 
      University of California Los Angeles, PO Box 951752, Los Angeles, CA, USA.
FAU - Zhang, Qiuheng
AU  - Zhang Q
AD  - Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, 
      University of California Los Angeles, PO Box 951752, Los Angeles, CA, USA.
FAU - Reed, Elaine F
AU  - Reed EF
AD  - Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, 
      University of California Los Angeles, PO Box 951752, Los Angeles, CA, USA.
FAU - Tsai, Eileen W
AU  - Tsai EW
AD  - 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.
LA  - eng
GR  - R01 AI042819/AI/NIAID NIH HHS/United States
GR  - T32 DK104687/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160405
PL  - Germany
TA  - Pediatr Nephrol
JT  - Pediatric nephrology (Berlin, Germany)
JID - 8708728
RN  - 0 (HLA Antigens)
RN  - 0 (Peptide Fragments)
RN  - 0 (Proteasome Inhibitors)
RN  - 69G8BD63PP (Bortezomib)
RN  - 80295-50-7 (Complement C4b)
RN  - 80295-52-9 (complement C4d)
SB  - IM
MH  - Adolescent
MH  - Bortezomib/*therapeutic use
MH  - Child, Preschool
MH  - Complement C4b/immunology
MH  - Female
MH  - Graft Rejection/*drug therapy
MH  - Graft Survival/drug effects
MH  - HLA Antigens/immunology
MH  - Humans
MH  - *Kidney Transplantation
MH  - Male
MH  - Peptide Fragments/immunology
MH  - Proteasome Inhibitors/*therapeutic use
MH  - Retrospective Studies
MH  - Young Adult
PMC - PMC5590841
MID - NIHMS902284
OTO - NOTNLM
OT  - Antibody-mediated rejection
OT  - Bortezomib
OT  - Kidney
OT  - Non-adherence
OT  - Pediatric
OT  - Proteasome inhibitor
OT  - Transplant
COIS- Conflict of Interest: The authors declare that they have no conflict of interest.
EDAT- 2016/04/07 06:00
MHDA- 2017/09/19 06:00
PMCR- 2017/09/08
CRDT- 2016/04/07 06:00
PHST- 2015/10/05 00:00 [received]
PHST- 2015/12/30 00:00 [accepted]
PHST- 2015/12/28 00:00 [revised]
PHST- 2016/04/07 06:00 [entrez]
PHST- 2016/04/07 06:00 [pubmed]
PHST- 2017/09/19 06:00 [medline]
PHST- 2017/09/08 00:00 [pmc-release]
AID - 10.1007/s00467-016-3319-3 [pii]
AID - 10.1007/s00467-016-3319-3 [doi]
PST - ppublish
SO  - Pediatr Nephrol. 2016 Aug;31(8):1341-8. doi: 10.1007/s00467-016-3319-3. Epub 2016 
      Apr 5.