Safety and Long-Term Efficacy of Eculizumab in a Renal Transplant Patient with Recurrent Atypical Hemolytic–Uremic Syndrome

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

doi:10.1111/j.1600-6143.2009.02817.x

Cited by 102 publications

(33 citation statements)

References 4 publications

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“…Eculizumab is a monoclonal antibody that binds C5, prohibiting its division into C5a and C5b; C5a acts as an anaphylatoxin, and C5b initiates the formation of the MAC/C5b-9 with the coordination of C6-C9. Prevention of the formation of C5a and MAC/C5b-9 inhibits complement-mediated thrombotic microangiopathy [14-20]. Eculizumab first received approval for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) in 2007 [14, 19-21] followed by multiple retrospective and prospective trials enrolling adult, adolescent or pediatric patients with aHUS.…”

Section: Discussionmentioning

confidence: 99%

“…Prevention of the formation of C5a and MAC/C5b-9 inhibits complement-mediated thrombotic microangiopathy [14-20]. Eculizumab first received approval for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) in 2007 [14, 19-21] followed by multiple retrospective and prospective trials enrolling adult, adolescent or pediatric patients with aHUS. These trials led to an accelerated approval for the use of eculizumab for the treatment of pediatric and adult patients with aHUS in 2011.…”

Section: Discussionmentioning

confidence: 99%

“…These trials led to an accelerated approval for the use of eculizumab for the treatment of pediatric and adult patients with aHUS in 2011. Eculizumab resulted in elimination of the requirement for dialysis or plasma therapy, sustained improvement in the estimated glomerular filtration rate (eGFR), and hematologic parameters that correlate with aHUS disease activity [14-18, 22-24]. …”

Section: Discussionmentioning

confidence: 99%

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Role of the Skin Biopsy in the Diagnosis of Atypical Hemolytic Uremic Syndrome

Magro¹,

Momtahen

Mulvey

et al. 2015

The American Journal of Dermatopathology

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Introduction Atypical hemolytic uremic syndrome (aHUS) is a prototypic thrombotic microangiopathy attributable to complement dysregulation. In the absence of complement inhibition, progressive clinical deterioration occurs. We postulated that a biopsy of normal skin could corroborate the diagnosis of aHUS via the demonstration of vascular deposits of C5b-9. Materials and methods Biopsies of normal skin from 22 patients with and without aHUS were processed for routine light microscopy as well as immunofluorescent studies. An assessment was made for vascular C5b-9 deposition immunohistochemically and by immunofluorescence. The biopsies were obtained primarily from the forearm and or deltoid. Results Patients with classic features of atypical HUS showed insidious microvascular changes including loose luminal platelet thrombi except in two patients in whom a striking thrombogenic vasculopathy was apparent in biopsied digital ulcers. Extensive microvascular deposits of the membrane attack complex (MAC)/ C5b-9 were identified excluding one patient in whom eculizumab was initiated prior to biopsy. In 5 of the 7 patients where follow-up was available, the patients exhibited an excellent treatment response to eculizumab. Patients without diagnostic clinical features of atypical HUS failed to show significant vascular deposits of complement except two patients with TTP including one in whom a Factor H mutation was identified. Conclusion In a clinical setting where aHUS is an important diagnostic consideration, extensive microvascular deposition of C5b-9 supports the diagnosis of either aHUS or a subset of TTP patients with concomitant complement dysregulation; significant vascular C5b-9 deposition predicts clinical responsiveness to eculizumab.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Role of the Skin Biopsy in the Diagnosis of Atypical Hemolytic Uremic Syndrome

Magro¹,

Momtahen

Mulvey

et al. 2015

The American Journal of Dermatopathology

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“…Including our patient, to date we found 21 cases reported in the literature of aHUS treated with eculizumab (table 3) [12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33]. Patients range in age from 1 month to 50 years at the time of treatment with eculizumab.…”

Section: Summary Of Case Reports In the Literature For Eculizumab Thementioning

confidence: 99%

Clinical Grand Rounds: Atypical Hemolytic Uremic Syndrome

Hodgkins

Bobrowski²,

Lane³

et al. 2012

Am J Nephrol

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Atypical hemolytic uremic syndrome (aHUS) is a rare, lifethreatening, chronic, genetic disease of uncontrolled alternative pathway complement activation. The understanding of the pathophysiology and genetics of this disease has expanded over recent decades and promising new developments in the management of aHUS have emerged. Regardless of the cause of aHUS, with or without a demonstrated mutation or autoantibody, blockade of terminal complement activation through C5 is of high interest as a mechanism to ameliorate the disease. Eculizumab, an existing monoclonal antibody directed against C5 with high affinity, prevents the perpetuation of the downstream activation of the complement cascade and the damage caused by generation of the anaphylotoxin C5a and the membrane attack complex C5b-9, by blocking C5 cleavage. We report the successful use of eculizumab in a patient after kidney transplantation and discuss the disease aHUS.

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“…Nurnberger et al [21] reported on an individual with a CFH mutation in whom PE had been unable to stop recurrent aHUS but who responded to treatment with eculizumab. Another patient with a C3 mutation who had received a renal transplant had recurrent disease which required PE to maintain aHUS remission [22]. In this individual, long-term treatment with eculizumab was used to replace PE to keep the patient disease free.…”

Section: Eculizumab In Renal Transplantationmentioning

confidence: 99%

Haemolytic Uraemic Syndrome

Kavanagh¹,

Goodship²

2010

Nephron Clin Pract

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Atypical haemolytic uraemic syndrome (aHUS) is a disease characterized by complement overactivation in which inherited defects in complement genes and acquired autoantibodies against complement regulatory proteins have been described. Identification of the underlying defect can both predict disease outcome and guide treatment. The ability to remove inhibitory autoantibodies and hyper-active complement components in addition to its ability to replace defective complement regulators means that plasma exchange is currently first-line therapy. In those with factor H and factor I mutations who do progress to end-stage renal failure, renal transplantation usually fails due to recurrent HUS. In this situation, combined liver-kidney transplantation has been suggested to correct the underlying genetic defect. Newer agents, such as the complement inhibitor eculizumab, may herald a new era in the treatment of aHUS.

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Safety and Long-Term Efficacy of Eculizumab in a Renal Transplant Patient with Recurrent Atypical Hemolytic–Uremic Syndrome

Cited by 102 publications

References 4 publications

Role of the Skin Biopsy in the Diagnosis of Atypical Hemolytic Uremic Syndrome

Role of the Skin Biopsy in the Diagnosis of Atypical Hemolytic Uremic Syndrome

Clinical Grand Rounds: Atypical Hemolytic Uremic Syndrome

Haemolytic Uraemic Syndrome

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