title: Eculizumab in an anephric patient with atypical haemolytic uraemic syndrome and advanced vascular lesions.
abstract: BACKGROUND
  Atypical haemolytic uraemic syndrome (aHUS) is associated with dysfunction of the alternative pathway of complement. Disease activity subsides as renal failure progresses but recurs upon renal transplantation, indicating that viable renal tissue contributes to disease activity. We present evidence of cerebrovascular occlusive disease indicating that vascular injury may occur in the absence of kidneys.
  
  
  METHODS
  A currently 12-year-old girl developed renal failure at the age of 20 months. She underwent bilateral nephrectomy and renal transplantation but lost the transplant due to recurrences. She was on haemodialysis for 7 years. At 10 years of age she developed a transient ischaemic attack. Imaging, genetic investigation and mutation characterization were performed.
  
  
  RESULTS
  Imaging demonstrated occlusion and stenosis of the carotid arteries. Two complement mutations, a novel mutation in factor B and a previously described mutation in factor I, and the H3-factor H haplotype, were identified. The factor B mutation, L433S, did not induce excessive complement activation in vitro. Measurement of C3 degradation products indicated ongoing complement activation. In spite of the patient being anephric, treatment was initiated with eculizumab, a humanized anti-C5 antibody that blocks terminal complement activation. She underwent a successful kidney transplant 9 months later and has not developed a recurrence or progression of vascular stenosis 1 year later.
  
  
  CONCLUSIONS
  The course of disease in this patient with aHUS suggests that complement-mediated vascular injury may occur in the total absence of renal tissue and overt recurrences. To our knowledge, this is the first description of eculizumab treatment in an anephric aHUS patient.
authors.affiliation: Department of Pediatrics, Clinical Sciences Lund, Lund University, Lund, Sweden.
authors.forename: Zivile D
authors.initials: ZD
authors.lastname: Békássy
authors.forename: Ann-Charlotte
authors.initials: AC
authors.lastname: Kristoffersson
authors.forename: Mats
authors.initials: M
authors.lastname: Cronqvist
authors.forename: Lubka T
authors.initials: LT
authors.lastname: Roumenina
authors.forename: Tania
authors.initials: T
authors.lastname: Rybkine
authors.forename: Laura
authors.initials: L
authors.lastname: Vergoz
authors.forename: Christophe
authors.initials: C
authors.lastname: Hue
authors.forename: Veronique
authors.initials: V
authors.lastname: Fremeaux-Bacchi
authors.forename: Diana
authors.initials: D
authors.lastname: Karpman
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D065766:Atypical Hemolytic Uremic Syndrome; D002561:Cerebrovascular Disorders / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D002648:Child; D003182:Complement C5 / Q000378:metabolism; D011415:Complement Factor B / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006463:Hemolytic-Uremic Syndrome / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D006801:Humans; D016030:Kidney Transplantation; D008279:Magnetic Resonance Imaging; D009154:Mutation / Q000235:genetics; D009392:Nephrectomy / Q000009:adverse effects*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D051437:Renal Insufficiency / Q000150:complications* / Q000601:surgery; D020349:Surface Plasmon Resonance
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003182:Complement C5; C481642:eculizumab; D011415:Complement Factor B
keywords: complement factor B; complement factor I; eculizumab; haemolytic uraemic syndrome; transient ischaemic attack