Eculizumab for paediatric patients with atypical haemolytic uraemic syndrome: full dataset analysis of post-marketing surveillance in Japan

Ito, Shuichi; Hataya, Hiroshi; Ashida, Akira; Hamada, Riku; Ishikawa, Tomoaki; Ishikawa, Yumiko; Shimono, Akihiko; Konomoto, Takao; Miyazawa, Tomoki; Ogura, Masao; Tanaka, Kazuki; Kubo, Shoji

doi:10.1093/ndt/gfac150

Cited by 8 publications

(2 citation statements)

References 39 publications

(71 reference statements)

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“…A haematologic normalization was defined as platelet count normalization (≥150 × 10 9 /L) and LDH normalization (˂1.5 times the age-matched upper limit of normal). Each normalization should be maintained for ≥4 weeks [ 29 ].…”

Section: Methodsmentioning

confidence: 99%

Immunosuppressive Therapy of Antibody-Mediated aHUS and TTP

Kelen,

Horváth,

Kis

et al. 2023

IJMS

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The recent classification of pediatric thrombotic microangiopathies (TMA) takes into consideration mechanisms of disease for guidance to targeted therapies. We present our experience with seven patients with antibody mediated atypical hemolytic uremic syndrome (aHUS) and thrombotic thrombocytopenic purpura (TTP). Five children had aHUS with antibodies against complement factor H (CFH-ab) and two with TTP with antibodies against metalloproteinase ADAMTS13. In the aHUS cases diagnosed and treated before the eculizumab era, CFH-ab was detected using the ELISA assay. Mutational analysis of selected complement genes was performed. TTP was diagnosed if, in addition to microangiopathic hemolytic anemia and thrombocytopenia, ischemic organ involvement and severe deficiency in ADAMTS13 activity were present. Treatment protocol consisted of plasma exchanges (PE) and steroid pulses, followed by the combination of cyclophosphamide and rituximab to achieve long-term immunosuppression. Four patients with CFH-ab and the TTP patients with ADAMTS13 antibodies came into sustained remission. After a median follow-up of 11.7 (range 7.7–12.9) years without maintenance therapy, no disease recurrence was observed; nevertheless, six patients, two had hypertension and two had proteinuria as a late consequence. One patient, with late diagnosis of CFH-ab and additional genetic risk factors who was treated only with PE and plasma substitution, reached end-stage renal disease and was later successfully transplanted using eculizumab prophylaxis. In the cases of antibody-mediated TMAs, PE and early immunosuppressive treatment may result in sustained remission with preserved kidney function. Further data are needed to establish optimal treatment of anti-FH antibody-associated HUS.

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Section: Methodsmentioning

confidence: 99%

Immunosuppressive Therapy of Antibody-Mediated aHUS and TTP

Kelen,

Horváth,

Kis

et al. 2023

IJMS

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“…While plasma therapy has long been a mainstay of treatment, newer studies support the use of eculizumab, a monoclonal antibody that binds to and inhibits complement C5 [5]. Eculizumab has proven more effective in preventing long-and short-term renal outcomes and reducing relapse rates [6,7]. In this report, we detail the case of a 36-year-old woman who presented at 36 weeks of gestation with breech presentation and HUS triggered by placental abruption.…”

Section: Introductionmentioning

confidence: 97%

Successful Management of Atypical Hemolytic-Uremic Syndrome in Pregnancy Using Eculizumab: A Case Review

Altaf,

Khanzada,

Qasim

et al. 2024

Cureus

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Hemolytic-uremic syndrome (HUS) is a rare thrombotic microangiopathy characterized by the triad of microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and acute kidney injury. The disease is pathologically marked by fibrinoid necrosis within renal arterioles and glomerular capillaries. HUS can be categorized into typical variants, often linked to Shiga toxin-producing Escherichia coli (STEC) infection, and atypical variants that stem from dysregulation in the alternative complement pathway. Pregnancy is a recognized predisposing condition for HUS due to the potential reduction in complement regulatory proteins and the possibility of heightened maternal immune response. This report illustrates the case of a 36-yearold woman who, at 36 weeks of gestation, faced a breech presentation and was diagnosed with atypical HUS (aHUS) after placental abruption. Following a cesarean section, she developed complications, including a pelvic hematoma and bilateral hydronephrosis. Despite initial suboptimal response to plasmapheresis, the patient exhibited marked clinical improvement with eculizumab treatment, with no evidence of disease relapse.

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