title: Efficacy and safety of eculizumab in childhood atypical hemolytic uremic syndrome in Japan.
abstract: BACKGROUND
  Atypical hemolytic uremic syndrome (aHUS) is a severe life-threatening disease with frequent progression to end-stage renal disease (ESRD). Eculizumab, a humanized anti-C5 monoclonal antibody targeting the activated complement pathway, has recently been introduced as a novel therapy against aHUS. We, therefore, investigated the efficacy and safety of eculizumab in Japanese pediatric patients.
  
  
  METHODS
  We retrospectively analyzed clinical course and laboratory data of the first ten children with aHUS treated with eculizumab nationwide.
  
  
  RESULTS
  Seven patients were resistant to plasma therapy and three were dependent on it. Causative gene mutations were found in five patients. Two patients had anti-complement factor H autoantibody. Three patients had a family history of thrombotic microangiopathy (TMA). After initiation of eculizumab, all patients immediately achieved hematological remission and could successfully discontinue plasma therapy. The median periods to normalization of platelet count, lactate dehydrogenase levels and disappearance of schistocytes were 5.5, 17 and 12 days, respectively. Nine patients recovered their renal function and the median period to terminate renal replacement therapy (RRT) was 3 days. However, two patients progressed to ESRD and required chronic RRT at the last observation. No patients had a relapse of TMA under regular eculizumab therapy. No serious adverse events occurred during the follow-up period.
  
  
  CONCLUSIONS
  Eculizumab is efficacious and well-tolerated therapy for children with aHUS. Although pathogenic mutations could not be detected in five patients, all patients showed immediate normalization of hematological abnormalities, strongly suggesting complement-related aHUS. This prompt hematological amelioration can become an indicator for therapeutic efficacy of eculizumab. However, appropriate indications and optimal duration of the treatment remain unclear.
authors.affiliation: Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8583, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Ito
authors.affiliation: Department of Pediatric Nephrology, Tokyo Metropolitan Children's Medical Center, 2-8-29 Musashidai, Fuchu, Tokyo, 183-8561, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hataya
authors.affiliation: Division of Nephrology and Rheumatology, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Saida
authors.affiliation: Department of Pediatrics, Nagano Red Cross Hospital, 5-22-1 Wakasato, Nagano, 380-8582, Japan.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Amano
authors.affiliation: Department of Pediatrics, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hidaka
authors.affiliation: Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University Graduate School of Medicine, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
authors.forename: Yaeko
authors.initials: Y
authors.lastname: Motoyoshi
authors.affiliation: Department of Pediatric Nephrology, Hiroshima Prefectural Hospital, 1-5-54 Ujina-Kanda, Minami-ku, Hiroshima, 734-8530, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Ohta
authors.affiliation: Department of Pediatric Nephrology, Tokyo Metropolitan Children's Medical Center, 2-8-29 Musashidai, Fuchu, Tokyo, 183-8561, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Department of Pediatric Nephrology, Tokyo Metropolitan Children's Medical Center, 2-8-29 Musashidai, Fuchu, Tokyo, 183-8561, Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Terano
authors.affiliation: Department of Pediatrics, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Iwasa
authors.affiliation: Department of Pediatric Nephrology, Tokyo Metropolitan Children's Medical Center, 2-8-29 Musashidai, Fuchu, Tokyo, 183-8561, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Kubota
authors.affiliation: Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8583, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Takada
authors.affiliation: Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8583, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Hara
authors.affiliation: Department of Blood Transfusion Medicine, Nara Medical University, 840 Shijo, Kashihara, Nara, 634-8521, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fujimura
authors.affiliation: Division of Nephrology and Rheumatology, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan. itoshu@yokohama-cu.ac.jp.|Department of Pediatrics, Graduate School of Medicine, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan. itoshu@yokohama-cu.ac.jp.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Ito
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D065766:Atypical Hemolytic Uremic Syndrome / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D012189:Retrospective Studies
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C481642:eculizumab
keywords: Alternative complement pathway; Atypical hemolytic uremic syndrome; Children; Eculizumab; Plasma therapy