title: Eculizumab in atypical hemolytic uremic syndrome: long-term clinical course and histological findings.
abstract: Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy associated with defective regulation of the alternative complement pathway. The prognosis for patients with aHUS is poor, and plasma exchange represents the first-line therapy. Eculizumab is a humanized monoclonal anti-C5 antibody that prevents the activation of the terminal complement pathway. Here, we report the case of a 9-year-old girl with frequent relapsing aHUS due to heterozygous factor H mutation who was initially treated with plasma exchange three times per week with 150% plasma exchange volume. This treatment frequently caused allergic reactions and school absences. Because any reduction in the frequency of plasma exchange immediately induced relapses of the aHUS, treatment with eculizumab, 600 mg every 2 weeks, was started and plasma exchange completely stopped. On this drug regimen the patient showed no evidence of disease activity during a period of more than 24 months. Renal function improved, proteinuria disappeared, the number of antihypertensive medications could be decreased, and the quality of life increased substantially. The inhibition of the terminal complement pathway by eculizumab was also confirmed by renal biopsy, which showed the absence of thrombotic microangiopathy 2 months after the initiation of eculizumab therapy. This case illustrates the long-term favorable outcome of aHUS with eculizumab treatment.
authors.affiliation: Division of Paediatric Nephrology, Children's Hospital, University of Bern, 3010 Berne, Switzerland.
authors.forename: Sibylle
authors.initials: S
authors.lastname: Tschumi
authors.forename: Mathias
authors.initials: M
authors.lastname: Gugger
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Bucher
authors.forename: Magdalena
authors.initials: M
authors.lastname: Riedl
authors.forename: Giacomo D
authors.initials: GD
authors.lastname: Simonetti
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D065766:Atypical Hemolytic Uremic Syndrome; D002648:Child; D017242:Complement Factor H / Q000235:genetics; D005260:Female; D006463:Hemolytic-Uremic Syndrome / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology*; D006801:Humans; D009154:Mutation; D010951:Plasma Exchange
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D017242:Complement Factor H; C481642:eculizumab