Eculizumab in an Anephric Patient With Atypical Haemolytic Uraemic Syndrome and Advanced Vascular Lesions

Nephrol Dial Transplant. 2013 Nov;28(11):2899-907. doi: 10.1093/ndt/gft340. Epub 2013 Sep 5.

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.

Keywords: complement factor B; complement factor I; eculizumab; haemolytic uraemic syndrome; transient ischaemic attack.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Atypical Hemolytic Uremic Syndrome
  • Cerebrovascular Disorders / drug therapy*
  • Cerebrovascular Disorders / etiology
  • Cerebrovascular Disorders / pathology
  • Child
  • Complement C5 / metabolism
  • Complement Factor B / genetics
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Hemolytic-Uremic Syndrome / drug therapy*
  • Hemolytic-Uremic Syndrome / etiology
  • Hemolytic-Uremic Syndrome / pathology
  • Humans
  • Kidney Transplantation*
  • Magnetic Resonance Imaging
  • Mutation / genetics
  • Nephrectomy / adverse effects*
  • Polymerase Chain Reaction
  • Prognosis
  • Renal Insufficiency / complications*
  • Renal Insufficiency / surgery
  • Surface Plasmon Resonance

Substances

  • Antibodies, Monoclonal, Humanized
  • Complement C5
  • eculizumab
  • Complement Factor B