Eculizumab: Safety and Efficacy After 17 Months of Treatment in a Renal Transplant Patient With Recurrent Atypical Hemolytic-Uremic Syndrome: Case Report

Châtelet, Valérie; Lobbedez, Thierry; Frémeaux‐Bacchi, Véronique; Ficheux, Maxence; Ryckelynck, Jean-Philippe; Ligny, Bruno Hurault de

doi:10.1016/j.transproceed.2010.09.125

Cited by 83 publications

(76 citation statements)

References 5 publications

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“…Eculizumab was approved initially in the management of paroxysmal nocturnal hemoglobinuria (53) and has been recently approved by the Food and Drug Administration and European regulatory organizations for the treatment of aHUS. Several case reports have underlined its efficiency in the treatment of aHUS affecting the native kidneys or the renal graft and even in the management of severe typical HUS cases (28,(54)(55)(56)(57)(58)(59). At least three open-label prospective industry-sponsored studies assessing the use of eculizumab in adult patients with aHUS have been conducted, and their results have been published in part in abstracts.…”

Section: Tma In Pregnancy: the Great Paradigm Shiftmentioning

confidence: 99%

Obstetric Nephrology

Fakhouri

Vercel

Frémeaux‐Bacchi

2012

Clinical Journal of the American Society of Nephrology

145

121

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Summary AKI in pregnancy remains a cause of significant fetomaternal mortality and morbidity, particularly in developing countries. Hypertensive complications of pregnancy (preeclampsia/eclampsia or hemolysis, elevated liver enzymes, and low platelets count syndrome) are the leading cause of AKI in pregnancy worldwide. Thrombotic microangiopathy is another peculiar and devastating cause of AKI in pregnancy. During the last decade, our understanding, and in some cases, our management, of these causes of AKI in pregnancy has dramatically improved. For instance, convincing data have linked pre-eclampsia/eclampsia to an increase in circulating antiangiogenic factors soluble Flt 1 and endoglin, which induce endothelial cell dysfunction, hypertension, and proteinuria. Several distinct pathogenic mechanisms underlying thrombotic microangiopathy, including thrombotic microangiopathy occurring during pregnancy, have been established. Thrombotic microangiopathy, which can present as hemolytic uremic syndrome or thrombotic thrombocytopenic purpura, can be reclassified in four potentially overlapping subtypes: disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 deficiency-related thrombotic microangiopathy, complement alternative pathway dysregulation-related thrombotic microangiopathy, secondary thrombotic microangiopathy (verotoxin and antiangiogenic drugs), and thrombotic microangiopathy of undetermined mechanism. In most cases, pregnancy is only a precipitating factor for thrombotic microangiopathy. Treatment of thrombotic microangiopathy occurring during pregnancy should be tailored to the underlying pathogenic mechanism: (1) restoration of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 serum activity in the setting of thrombotic thrombocytopenic purpura through plasma exchanges and in some cases, B cell-depleting therapy and (2) inhibition of complement alternative pathway activation in atypical hemolytic uremic syndrome using antiC5 blocking antibody (eculizumab).

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Section: Tma In Pregnancy: the Great Paradigm Shiftmentioning

confidence: 99%

Obstetric Nephrology

Fakhouri

Vercel

Frémeaux‐Bacchi

2012

Clinical Journal of the American Society of Nephrology

145

121

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“…Chatelet ve ark. ilk olarak 2009 yılında böbrek naklinden üç yıl sonra nüks eden atipik HÜS vakasına plazmeferez sonrası Eculizumab tedavisi uygulamış ve başarılı sonuç almışlardır (13). Böbrek nakli sonrası tekrarlama riski yüksek olduğundan nakil sonrası dönemde profilaktik kullanımı gündeme gelmiştir.…”

Section: Eculizumabunclassified

Böbrek Naklinde Kullanılan Yeni İmmünsupresif İlaçlar

Güngör¹,

Alp²,

Pembegül³

et al. 2017

Turk Neph Dial Transpl

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ÖzSon dönem böbrek yetmezliğinin en seçkin tedavi yöntemi böbrek naklidir. Ne yazıkki akut-kronik rejeksiyonlar ve ilaç toksisiteleri nakil sonrası dönemde organ sağ kalımını kısaltmaktadır. Bu yüzden son yıllarda rejeksiyonları ve ilaç toksisitelerini azaltabilecek yeni ilaçların bulunması amaçlanmıştır. Biz bu derlemede son yıllarda böbrek naklinde kullanıma girmiş yeni immünsupresif ilaçların başlı-calarını özetlemeyi amaçladık. AnAhTAR sÖzcükleR: Böbrek nakli, Yeni, İmmünsupresif ilaçlar AbsTRAcTRenal transplantation is the most prominent treatment of end-stage renal failure. Unfortunately, acute and chronic rejections and drug toxicities reduce graft survival in the post-transplantation period. An attempt has therefore been made in recent years to develop new drugs that can reduce rejections and drug toxicities. In this review, we intended to summarize the new immunosuppressive drugs that have entered use in recent years. GİRİŞSon dönem böbrek yetmezliğinin en seçkin tedavi yöntemi böbrek naklidir. Başarılı bir böbrek nakli için, gerek indüksiyon, gerekse idame immünsupresif tedavinin hasta bazında bireyselleştirilmesi gerekir. Halen dünyada indüksiyon tedavisi için en sık Antitimosit globulin (ATG), idame tedavide ise kortikosteroid-kalsinörin inhibitörü-antimetabolit ilaç kombinasyonu tercih edilmektedir. Günümüzde halen akut hücresel ve humoral rejeksiyonlar ne yazıkki böbrek sağ kalımını olumsuz etkileyen önemli sorunlar olarak karşımıza çıkmaya devam etmektedir. bir yıllık graft sürveyi %90'ların üzerinde iken beş yıllık sürvey %72 civarındadır. Uzun süreli kullanımda ilaçların toksik etkilerinin ortaya çıkması son 10 yıl içerisinde böbrek naklinde indüksiyon ve idame tedavide farklı ajanların bulunması için bir gereklilik doğurmuştur. Özellikle böbrek nakli tedavisinin köşetaşı ilacı olan kalsinörin inhibitörlerinin iki yıldan uzun süre kullanımında yüksek oranda toksisite gelişimi bu ihtiyacı zorunlu hale getirmiştir. Biz bu yazıda böbrek nakli hastalarında son yıllarda deneme aşamasında olan ve/veya kullanılmaya başlanan yeni immünsupresif ilaçların genel özelliklerini ve böbrek naklindeki deneyimlerini sunmayı amaçladık. eculizumabEculizumab insanlaştırılmış bir monoklonal IgG2/4 antikordur. Kompleman C5 proteinine bağlanarak C5 konvertaz ile C5a ve C5b'ye yıkımını önleyerek membran atak kompleksi oluşumunu engeller ve kompleman aracılı hücre hasarına engel olur (1). Eculizumab temelde terminal kompleman kaskadını hedefler, ancak proksimal kompleman yolaklarının etkisini ortadan kaldıramayabilir.

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“…Factor H synthesised in the liver and CD46, a transmembrane protein, are the commonest mutations found in aHUS that result in intrarenal thrombosis and haemolysis as the complement pathways are largely unregulated post-transplant. Eculizumab has been revolutionary in these patients allowing successful transplantation in this cohort of patients [125][126][127][128]. Eculizumab is also being tested for the prevention of delayed graft function (NCT01403389).…”

Section: Target -Systemic Complementmentioning

confidence: 99%

Complement—here, there and everywhere, but what about the transplanted organ?

Montero

Sacks

Smith

2016

Seminars in Immunology

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The part of the innate immune system that communicates and effectively primes the adaptive immune system was termed "complement" by Ehrlich to reflect its complementarity to antibodies having previously been described as "alexine" (i.e protective component of serum) by Buchner and Bordet. It has been established that complement is not solely produced systemically but may have origin in different tissues where it can influence organ specific functions that may affect the outcome of transplanted organs. This review looks at the role of complement in particular to kidney transplantation. We look at current literature to determine whether blockade of the peripheral or central compartments of complement production may prevent ischaemic reperfusion injury or rejection in the transplanted organ.We also review new therapeutics that have been developed to inhibit components of the complement cascade with varying degrees of success leading to an increase in our understanding of the multiple triggers of this complex system. In addition, we consider whether biomarkers in this field are effective markers of disease or treatment. Word count 169

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Eculizumab: Safety and Efficacy After 17 Months of Treatment in a Renal Transplant Patient With Recurrent Atypical Hemolytic-Uremic Syndrome: Case Report

Cited by 83 publications

References 5 publications

Obstetric Nephrology

Obstetric Nephrology

Böbrek Naklinde Kullanılan Yeni İmmünsupresif İlaçlar

Complement—here, there and everywhere, but what about the transplanted organ?

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