Use of Belatacept as Alternative Immunosuppression in Three Renal Transplant Patients with<i>De Novo</i>Drug-Induced Thrombotic Microangiopathy

Cicora, Federico; Paz, Marta; Mos, Fernando; Roberti, Javier

doi:10.1155/2013/260254

Cited by 19 publications

(11 citation statements)

References 15 publications

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“… Case series: 29 patients with de novo TMA treated with discontinuation of CNI and PEX: graft salvage rate was 80% [ 72 ]. Case reports of TMA resolution following immunosuppression switch, CNI to belatacept [ 73 ] or everolimus [ 74 ]. 2 cases of TMA following PAK transplant successfully treated with PEX and immunosuppression switch [ 75 ].…”

Section: Evidence For the Role Of Complement In The Tmasmentioning

confidence: 99%

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Complement C5-inhibiting therapy for the thrombotic microangiopathies: accumulating evidence, but not a panacea

Brocklebank

Kavanagh

2017

Clinical Kidney Journal

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Thrombotic microangiopathy (TMA), characterized by organ injury occurring consequent to severe endothelial damage, can manifest in a diverse range of diseases. In complement-mediated atypical haemolytic uraemic syndrome (aHUS) a primary defect in complement, such as a mutation or autoantibody leading to over activation of the alternative pathway, predisposes to the development of disease, usually following exposure to an environmental trigger. The elucidation of the pathogenesis of aHUS resulted in the successful introduction of the complement inhibitor eculizumab into clinical practice. In other TMAs, although complement activation may be seen, its role in the pathogenesis remains to be confirmed by an interventional trial. Although many case reports in TMAs other than complement-mediated aHUS hint at efficacy, publication bias, concurrent therapies and in some cases the self-limiting nature of disease make broader interpretation difficult. In this article, we will review the evidence for the role of complement inhibition in complement-mediated aHUS and other TMAs.

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Section: Evidence For the Role Of Complement In The Tmasmentioning

confidence: 99%

“…Case reports of TMA resolution following immunosuppression switch, CNI to belatacept [ 73 ] or everolimus [ 74 ].…”

Section: Evidence For the Role Of Complement In The Tmasmentioning

confidence: 99%

Complement C5-inhibiting therapy for the thrombotic microangiopathies: accumulating evidence, but not a panacea

Brocklebank

Kavanagh

2017

Clinical Kidney Journal

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“…Although the use of belatacept is associated with an increased risk of aTCMR, it has been shown to be a good alternative in KTRs with a contraindication to CNIs. Multiple studies have reported successful conversion to belatacept in KTRs with CNI-induced nephrotoxicity, impaired allograft function, delayed graft function, CNI-mediated thrombotic microangiopathy, or atypical hemolytic uremic syndrome [65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80][81][82]. Furthermore, KTRs with poorly controlled diabetes mellitus while receiving CNI therapy may benefit from belatacept [83,84].…”

Section: Clinical Outcomes After Conversion To Belatacept In Kidney Tmentioning

confidence: 99%

Costimulation Blockade in Kidney Transplant Recipients

Zwan

Hesselink

Hoogen

et al. 2019

Drugs

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Costimulation between T cells and antigen-presenting cells is essential for the regulation of an effective alloimmune response and is not targeted with the conventional immunosuppressive therapy after kidney transplantation. Costimulation blockade therapy with biologicals allows precise targeting of the immune response but without non-immune adverse events. Multiple costimulation blockade approaches have been developed that inhibit the alloimmune response in kidney transplant recipients with varying degrees of success. Belatacept, an immunosuppressive drug that selectively targets the CD28-CD80/CD86 pathway, is the only costimulation blockade therapy that is currently approved for kidney transplant recipients. In the last decade, belatacept therapy has been shown to be a promising therapy in subgroups of kidney transplant recipients; however, the widespread use of belatacept has been tempered by an increased risk of acute kidney transplant rejection. The purpose of this review is to provide an overview of the costimulation blockade therapies that are currently in use or being developed for kidney transplant indications.

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“…The first case report in 2009 documented TMA resolution after belatacept therapy used for immunosuppression in post-transplantation TMA due to CNI-induced endothelial toxicity[ 138 ]. Two case series have followed, thereafter documenting fair graft outcome due to resolution of the CNI-induced TMA[ 139 , 140 ]. Of note, belatacept has nothing to do with the underlying endothelial derangement, its role is only to replace/displace the culprit drug[ 2 ]; and (4) Complement inhibition: Eculizumab, an anti-C5 agent, blocks the lytic C5b-9 membrane attack complex generation.…”

Section: Therapy Of Post-transplant Tmamentioning

confidence: 99%

Thrombotic microangiopathy after renal transplantation: Current insights inde novoand recurrent disease

Abbas¹,

Kossi

Kim

et al. 2018

WJT

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Thrombotic microangiopathy (TMA) is one of the most devastating sequalae of kidney transplantation. A number of published articles have covered either de novo or recurrent TMA in an isolated manner. We have, hereby, in this article endeavored to address both types of TMA in a comparative mode. We appreciate that de novo TMA is more common and its prognosis is poorer than recurrent TMA; the latter has a genetic background, with mutations that impact disease behavior and, consequently, allograft and patient survival. Post-transplant TMA can occur as a recurrence of the disease involving the native kidney or as de novo disease with no evidence of previous involvement before transplant. While atypical hemolytic uremic syndrome is a rare disease that results from complement dysregulation with alternative pathway overactivity, de novo TMA is a heterogenous set of various etiologies and constitutes the vast majority of post-transplant TMA cases. Management of both diseases varies from simple maneuvers, e.g., plasmapheresis, drug withdrawal or dose modification, to lifelong complement blockade, which is rather costly. Careful donor selection and proper recipient preparation, including complete genetic screening, would be a pragmatic approach. Novel therapies, e.g., purified products of the deficient genes, though promising in theory, are not yet of proven value.

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Use of Belatacept as Alternative Immunosuppression in Three Renal Transplant Patients withDe NovoDrug-Induced Thrombotic Microangiopathy

Cited by 19 publications

References 15 publications

Complement C5-inhibiting therapy for the thrombotic microangiopathies: accumulating evidence, but not a panacea

Complement C5-inhibiting therapy for the thrombotic microangiopathies: accumulating evidence, but not a panacea

Costimulation Blockade in Kidney Transplant Recipients

Thrombotic microangiopathy after renal transplantation: Current insights inde novoand recurrent disease

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