Proteasome inhibition with bortezomib: an effective therapy for severe antibody mediated rejection after renal transplantation

Sureshkumar, Kalathil K; Hussain, Sultana Monira; Marcus, Richard J.; Ko, Tina Y; Khan, Rafeeq Alam; Tom, Kusum; Vivas, Carlos; Parris, George L.; Jasnosz, Katherine M.; Thai, Ngoc

doi:10.5414/cn107156

Cited by 34 publications

(31 citation statements)

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“…2 AMR is now recognized as a major cause for graft loss after solid organ transplant. 3 As preformed donor-specific anti-HLA antibodies (DSA), de novo DSA contribute to poor outcomes by increasing the risk of allograft rejections, cardiac allograft vasculopathy (CAV), and death.…”

mentioning

confidence: 99%

Late antibody-mediated rejection after heart transplantation: Mortality, graft function, and fulminant cardiac allograft vasculopathy

Coutance

Ouldamar

Rouvier³

et al. 2015

The Journal of Heart and Lung Transplantation

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mentioning

confidence: 99%

Late antibody-mediated rejection after heart transplantation: Mortality, graft function, and fulminant cardiac allograft vasculopathy

Coutance

Ouldamar

Rouvier³

et al. 2015

The Journal of Heart and Lung Transplantation

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“…4 The first step is plasmapheresis, which helps not only in removing previously secreted antibodies but also, in increasing the metabolic demands on memory B cells and plasma cells and thereby, enhancing their susceptibility to proteasome inhibition. 5,6 The usual prescription includes 1.0 to 1.5 volume exchange using albumin solution daily or on alternate days, continued until serum creatinine falls within 30% of previous baseline values. This modality does not suppress antibody production and in fact, can cause a rebound in DSA levels after plasmapheresis.…”

Section: Discussionmentioning

confidence: 99%

Treatment of Antibody-Mediated Rejection in Kidney Transplant Recipients: A Single-Center Experience With a Bortezomib-Based Regimen

Nigos

Arora²,

Nath³

et al. 2012

Exp Clin Transplant

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Objectives: Antibody-mediated rejection after kidney transplant is less responsive to conventional antirejection therapies. The proteasome inhibitor bortezomib has activity against mature plasma cells that produce damaging donor-specific antibodies. We present our experience of using a bortezomibbased regimen in patients with severe antibodymediated rejection. Conclusions:In this series, we demonstrated the effectiveness of a bortezomib-based treatment regimen in achieving reduction of donor-specific antibody titers and stable renal function in patients experiencing severe antibody-mediated rejection.

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“…Currently, it is only approved for use in multiple myeloma and mantle cell lymphoma; however, success in reduction of DSAs and treatment of ABMR for solid organ transplant has been demonstrated in large studies [78,79]. Adult kidney transplant rejection studies have shown variable results for success when measured in terms of decreased DSAs, histological improvement, and/or improvement in graft function [80][81][82][83][84][85]. However, the cases that showed no response in graft function had improvements in DSA levels, but TPE was also used and follow-up was short, which may not have allowed enough time for reconstitution of DSAs.…”

Section: Cell Depletionmentioning

confidence: 99%

Antibody-Mediated Rejection in Pediatric Kidney Transplantation: Pathophysiology, Diagnosis, and Management

Singh

Sarwal

2015

Drugs

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Kidney transplant is the preferred treatment of pediatric end-stage renal disease. One of the most challenging aspects of pediatric kidney transplant is the prevention and treatment of antibody-mediated rejection (ABMR), which is one of the main causes of graft dysfunction and early graft loss. Most challenges are similar to those faced in adult kidney transplants; however, factors unique to the pediatric realm include naivety of the immune system and the small number of studies and randomized controlled trials available when considering pharmacological treatment options. Here, we present a case of ABMR in a pediatric patient and a review of the pathophysiology, diagnosis, and management of ABMR. ABMR in pediatric kidney transplant continues to be a frustrating condition to treat because (1) there still remain many unidentified potential antigens leading to ABMR, (2) children and adults are at different stages of their immune system development, and, thus, (3) the full pathophysiology of alloimmunity is still not completely understood, and (4) the efficacy and safety of treatment in adults may not be directly translated to children. As we continue to gain a better understanding towards the precise alloimmune mechanism that drives a particular ABMR, we can also improve pharmacotherapeutic choices. With continued research, they will become more precise in treating a particular mechanism versus using a broad scope of immunosuppression such as steroids. However, there is much more to be uncovered, such as identifying more non-human leukocyte antigens and their role in alloimmunity, determining the exact mechanism of adults achieving complete operational tolerance, and understanding the difference between pediatric and adult transplant recipients. Making strides towards a better understanding of these mechanisms will lead to continued efficacy and safety in treatment of pediatric ABMR.

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Proteasome inhibition with bortezomib: an effective therapy for severe antibody mediated rejection after renal transplantation

Cited by 34 publications

References 0 publications

Late antibody-mediated rejection after heart transplantation: Mortality, graft function, and fulminant cardiac allograft vasculopathy

Late antibody-mediated rejection after heart transplantation: Mortality, graft function, and fulminant cardiac allograft vasculopathy

Treatment of Antibody-Mediated Rejection in Kidney Transplant Recipients: A Single-Center Experience With a Bortezomib-Based Regimen

Antibody-Mediated Rejection in Pediatric Kidney Transplantation: Pathophysiology, Diagnosis, and Management

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