Lack of Efficacy and Safety of Eculizumab for Treatment of Antibody-Mediated Rejection Following Renal Transplantation

Heo, Sujung; Park, Youngchan; Lee, Nagyeom; Kim, Yanghyeon; Kim, Ye Na; Shin, Ho Sik; Jung, Yeonsoon; Rim, Hark; Rennke, Helmut G.; Chandraker, Anil

doi:10.1016/j.transproceed.2022.08.008

Cited by 3 publications

(4 citation statements)

References 35 publications

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“…It concluded that eculizumab alone was ineffective for AMR treatment or prevention of AMR progressing to chronic AMR or transplant glomerulopathy compared to standard of care. 46 All patients were on similar maintenance immunosuppression regimen (Tacrolimus + Mycophenolate mofetil + Prednisolone). Mean time to the diagnosis of AMR was 1415 days and all cases had positive C4d staining.…”

Section: Eculizumab As First-line Treatment Of Early-onset Acute Amrmentioning

confidence: 99%

“…AMR, antibody mediated rejection; HLA, human leukocyte antigen; HUS, hemolytic uremic syndrome; MAC, membrane attack complex; mTOR, mammalian target of rapamycin; NK, natural killer; TMA, thrombotic microangiopathy. of the followings 1 : anti-HLA (DSA) antibodies, 2 histopathological findings consistent with Banff class II or III AMR, 3 peritubular capillary C4d positive staining, 46 while patients with histopathological findings of nonacute AMR or interstitial fibrosis or tubular atrophy were excluded from the study.…”

Section: Eculizumab As First-line Treatment Of Early-onset Acute Amrmentioning

confidence: 99%

“…Mean time to the diagnosis of AMR was 1415 days and all cases had positive C4d staining. Inclusion criteria were the presence of at least two of the followings 1 : anti‐HLA (DSA) antibodies, 2 histopathological findings consistent with Banff class II or III AMR, 3 peritubular capillary C4d positive staining, 46 while patients with histopathological findings of nonacute AMR or interstitial fibrosis or tubular atrophy were excluded from the study.…”

Section: Clinical Experience With Eculizumab In the Treatment Of Anti...mentioning

confidence: 99%

“…A multicenter randomized open‐label clinical study enrolled 11 participants, seven treated with eculizumab and four with standard of care (Plasmapheresis/IVIG). It concluded that eculizumab alone was ineffective for AMR treatment or prevention of AMR progressing to chronic AMR or transplant glomerulopathy compared to standard of care 46 . All patients were on similar maintenance immunosuppression regimen (Tacrolimus + Mycophenolate mofetil + Prednisolone).…”

Section: Clinical Experience With Eculizumab In the Treatment Of Anti...mentioning

confidence: 99%

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The role of anticomplement therapy in the management of the kidney allograft

Kanbay,

Copur,

Yilmaz

et al. 2024

Clinical Transplantation

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As the number of patients living with kidney failure grows, the need also grows for kidney transplantation, the gold standard kidney replacement therapy that provides a survival advantage. This may result in an increased rate of transplantation from HLA‐mismatched donors that increases the rate of antibody‐mediated rejection (AMR), which already is the leading cause of allograft failure. Plasmapheresis, intravenous immunoglobulin therapy, anti‐CD20 therapies (i.e., rituximab), bortezomib and splenectomy have been used over the years to treat AMR as well as to prevent AMR in high‐risk sensitized kidney transplant recipients. Eculizumab and ravulizumab are monoclonal antibodies targeting the C5 protein of the complement pathway and part of the expanding field of anticomplement therapies, which is not limited to kidney transplant recipients, and also includes complement‐mediated microangiopathic hemolytic anemia, paroxysmal nocturnal hemoglobinuria, and ANCA‐vasculitis. In this narrative review, we summarize the current knowledge concerning the pathophysiological background and use of anti‐C5 strategies (eculizumab and ravulizumab) and C1‐esterase inhibitor in AMR, either to prevent AMR in high‐risk desensitized patients or to treat AMR as first‐line or rescue therapy and also to treat de novo thrombotic microangiopathy in kidney transplant recipients.

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Section: Eculizumab As First-line Treatment Of Early-onset Acute Amrmentioning

confidence: 99%

Section: Eculizumab As First-line Treatment Of Early-onset Acute Amrmentioning

confidence: 99%

Section: Clinical Experience With Eculizumab In the Treatment Of Anti...mentioning

confidence: 99%

Section: Clinical Experience With Eculizumab In the Treatment Of Anti...mentioning

confidence: 99%

See 2 more Smart Citations

The role of anticomplement therapy in the management of the kidney allograft

Kanbay,

Copur,

Yilmaz

et al. 2024

Clinical Transplantation

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Targeting the Complement Pathway in Kidney Transplantation

Golshayan

Schwotzer

Fakhouri

2023

JASN

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The complement system is paramount in the clearance of pathogens and cell debris, yet is increasingly recognized as a key component in several pathways leading to allograft injury. There is thus a growing interest in new biomarkers to assess complement activation and guide tailored therapies after kidney transplantation. C5 blockade has revolutionized post-transplant management of atypical hemolytic uremic syndrome, a paradigm of complement-driven disease. Similarly, new drugs targeting the complement amplification loop hold much promise in the treatment and prevention of recurrence of C3 glomerulopathy. Although unduly activation of the complement pathway has been described following brain death and ischemia-reperfusion, any clinical attempts to mitigate the ensuing renal insults have so far provided mixed results. However, the intervention timing, strategy, and type of complement blocker need to be optimized in these settings. Furthermore, the fast-moving field of ex-vivo organ perfusion technology opens new avenues to deliver complement-targeted drugs to kidney allografts with limited iatrogenic risks. Complement plays also a key role in the pathogenesis of donor-specific ABO- and HLA-targeted alloantibodies. However, C5 blockade failed overall to improve outcomes in highly-sensitized patients and prevent the progression to chronic antibody-mediated rejection. Similarly, well-conducted studies with C1-inhibitor in sensitized recipients yielded disappointing results so far, in part due to subtherapeutic dosage used in clinical studies. The emergence of new complement blockers raises hope to significantly reduce the negative impact of ischemia-reperfusion, antibody-mediated rejection, and nephropathy recurrence on outcomes after kidney transplantation.

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The Complement System in Kidney Transplantation

Santarsiero

Aiello

2023

Cells

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Kidney transplantation is the therapy of choice for patients who suffer from end-stage renal diseases. Despite improvements in surgical techniques and immunosuppressive treatments, long-term graft survival remains a challenge. A large body of evidence documented that the complement cascade, a part of the innate immune system, plays a crucial role in the deleterious inflammatory reactions that occur during the transplantation process, such as brain or cardiac death of the donor and ischaemia/reperfusion injury. In addition, the complement system also modulates the responses of T cells and B cells to alloantigens, thus playing a crucial role in cellular as well as humoral responses to the allograft, which lead to damage to the transplanted kidney. Since several drugs that are capable of inhibiting complement activation at various stages of the complement cascade are emerging and being developed, we will discuss how these novel therapies could have potential applications in ameliorating outcomes in kidney transplantations by preventing the deleterious effects of ischaemia/reperfusion injury, modulating the adaptive immune response, and treating antibody-mediated rejection.

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Lack of Efficacy and Safety of Eculizumab for Treatment of Antibody-Mediated Rejection Following Renal Transplantation

Cited by 3 publications

References 35 publications

The role of anticomplement therapy in the management of the kidney allograft

The role of anticomplement therapy in the management of the kidney allograft

Targeting the Complement Pathway in Kidney Transplantation

The Complement System in Kidney Transplantation

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