Bortezomib for refractory acute antibody‐mediated rejection in kidney transplant recipients: A single‐centre case series

Sousa-Amorim, Erika De; Revuelta, Ignacio; Diekmann, Fritz; Cofan, Frederic; Lozano, Miguel; Cid, Joan; Palou, Eduard; Solé, Manel; Campistol, Josep M.; Oppenheimer, F

doi:10.1111/nep.12659

Cited by 13 publications

(16 citation statements)

References 23 publications

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“…It was FDA approved in 2008 for treatment of refractory multiple myeloma and has been successfully used in ABMR treatment in transplantation [35, 36]. Bortezomib inhibits the 26s proteasome which ultimately leads to plasma cell apoptosis.…”

Section: Therapeutic Approaches For Immunomodulation Of Hla Sensitmentioning

confidence: 99%

Desensitization: Overcoming the Immunologic Barriers to Transplantation

Sethi

Choi

Toyoda

et al. 2017

Journal of Immunology Research

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HLA (Human Leucocyte Antigen) sensitization is a significant barrier to successful kidney transplantation. It often translates into difficult crossmatch before transplant and increased risk of acute and chronic antibody mediated rejection after transplant. Over the last decade, several immunomodulatory therapies have emerged allowing for increased access to kidney transplantation for the immunologically disadvantaged group of HLA sensitized end stage kidney disease patients. These include IgG inactivating agents, anti-cytokine antibodies, costimulatory molecule blockers, complement inhibitors, and agents targeting plasma cells. In this review, we discuss currently available agents for desensitization and provide a brief analysis of data on novel biologics, which will likely improve desensitization outcomes, and have potential implications in treatment of antibody mediated rejection.

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Section: Therapeutic Approaches For Immunomodulation Of Hla Sensitmentioning

confidence: 99%

Desensitization: Overcoming the Immunologic Barriers to Transplantation

Sethi

Choi

Toyoda

et al. 2017

Journal of Immunology Research

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“…Recently, bortezomib, a proteasome inhibitor, has been used as a plasma cell-targeting agent during transplantation (6,7) and has been shown to reduce antibodies by depleting antibody-producing plasma cells and blocking anti-human leukocyte antigen (HLA) immunoglobulin G secretion. In previous studies, the use of bortezomib for the treatment of refractory AMR and primary treatment of AMR has also been reported (4,(8)(9)(10). These previous case series using bortezomib therapy as a treatment for refractory and primary AMR show that bortezomib can be an alternative treatment for such recipients.…”

Section: J Korean Soc Transplantㆍseptember 2018ㆍvolume 32ㆍissuementioning

confidence: 92%

“…AMR with various success rates (7,9,20,21). In these successful cases, treatment with bortezomib therapy showed reversal of graft rejection, improved renal allograft function, and decreased DSA levels.…”

Section: Several Transplant Centers Have Used Bortezomib To Treatmentioning

confidence: 99%

Bortezomib Treatment for Refractory Antibody-Mediated Rejection Superimposed with BK Virus-Associated Nephropathy during the Progression of Recurrent C3 Glomerulonephritis

Lee

Kim

et al. 2018

Korean J Transplant

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A 38-year-old man, who underwent a second kidney transplantation (KT), was admitted because of antibody-mediated rejection (AMR) complicated by BK virus-associated nephropathy (BKVAN). He was placed on hemodialysis at the age of 24 years because of membranoproliferative glomerulonephritis. At the age of 28 years, he underwent a living donor KT from his father; however, 1 year after the transplantation, he developed a recurrence of the primary glomerular disease, resulting in graft failure 2 years after the first KT. Ten years later, he received a deceased-donor kidney with a B-cell-positive-cross-match. He received 600 mg of rituximab before the KT with three cycles of plasmapheresis and immunoglobulin (0.5 g/kg) therapy after KT. During the follow-up, the first and second allograft biopsies at 4 and 10 months after KT revealed AMR with a recurrence of primary glomerular disease that was reclassified as C3 glomerulonephritis (C3GN). He received a steroid pulse, rituximab, plasmapheresis, and immunoglobulin therapies. The third allograft biopsy demonstrated that the BKVAN was complicated with AMR and C3GN. As the azotemia did not improve after repeated conventional therapies for AMR, one cycle of bortezomib (1.3 mg/m 2 ×4 doses) was administered. The allograft function stabilized, and BK viremia became undetectable after 6 months. The present case suggests that bortezomib therapy may be applicable to patients with refractory AMR, even in cases complicated with BKVAN.

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“…using proteasome inhibitors such as Bortezomib), or, as suggested by the classical model, indirectly, by depleting CD20 + B-cell precursors (using Rituximab) or CD4 + Th cells [using antithymocyte globulin (ATG)]. (11) Despite initial promising results in small cases series of early period AMR, (36,37) recent randomized control trials do not support Bortezomib efficacy in LpAMR. (38) While it is possible that this disparate responsiveness is due to cumulative irreversible damage in late rejection, differences in proteasome inhibitor responsiveness between early and late period AMR have also been reported.…”

Section: Therapeutic Options In Lpamrmentioning

confidence: 99%

Murder in the Cathedral: Antibodies and the Limits of Transplantation

Davies¹

2019

Wits Journal of Clinical Medicine

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Although transplantation is the optimal therapy for end-stage renal disease, long-term survival of kidney allografts remains elusive. Antibody-mediated rejection has been implicated as a major factor in late period graft loss. The refractory nature of late period antibody-mediated rejection is the evidence of an important immunological process with implications for other solid organ transplants and for other diseases. This review details advances in the understanding of late period antibody-mediated rejection in the context of local experience.

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Bortezomib for refractory acute antibody‐mediated rejection in kidney transplant recipients: A single‐centre case series

Abstract: Bortezomib could be useful as an adjuvant therapy for ABMR refractory to conventional treatment with acceptable mid-term outcomes in these severe cases. More research is needed to develop strategies to better preserve graft function after refractory ABMR.

Cited by 13 publications

References 23 publications

Desensitization: Overcoming the Immunologic Barriers to Transplantation

Desensitization: Overcoming the Immunologic Barriers to Transplantation

Bortezomib Treatment for Refractory Antibody-Mediated Rejection Superimposed with BK Virus-Associated Nephropathy during the Progression of Recurrent C3 Glomerulonephritis

Murder in the Cathedral: Antibodies and the Limits of Transplantation

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