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Bortezomib may stabilize pediatric renal transplant recipients with antibody-mediated rejection

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Abstract

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 m2 and the mean 1 year post-bortezomib eGFR was 53 ml/min/1.73 m2. 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.

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Funding

We would like to thank The Casey Lee Ball Foundation and the UCLA Children’s Discovery and Innovation Institute and The Today’s and Tomorrow’s Children Fund for supporting this work.

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Authors and Affiliations

  1. 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

    Meghan H. Pearl, Anjali B. Nayak, Robert B. Ettenger & Eileen W. Tsai

  2. Pediatric Nephrology and Transplant Immunology, Cedars Sinai Medical Center, Los Angeles, CA, USA

    Dechu Puliyanda

  3. Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, PO Box 951752, Los Angeles, CA, USA

    Miguel Fernando Palma Diaz, Qiuheng Zhang & Elaine F. Reed

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  1. Meghan H. Pearl
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  2. Anjali B. Nayak
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  3. Robert B. Ettenger
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  4. Dechu Puliyanda
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  5. Miguel Fernando Palma Diaz
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  8. Eileen W. Tsai
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Corresponding author

Correspondence to Meghan H. Pearl.

Ethics declarations

This retrospective chart review was performed in accordance with the UCLA institutional review board (IRB #11-003592) and formal patient consent is not required. Additionally, this report conforms with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

A related editorial commentary can be found at doi: 10.1007/s00467-016-3315-7.

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Pearl, M.H., Nayak, A.B., Ettenger, R.B. et al. Bortezomib may stabilize pediatric renal transplant recipients with antibody-mediated rejection. Pediatr Nephrol 31, 1341–1348 (2016). https://doi.org/10.1007/s00467-016-3319-3

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