Complement functional tests for monitoring eculizumab treatment in patients with atypical hemolytic uremic syndrome

J Thromb Haemost. 2014 Sep;12(9):1440-8. doi: 10.1111/jth.12615. Epub 2014 Jul 16.


Background: Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy characterized by hemolysis, platelet consumption, and renal injury. Eculizumab, a mAb that blocks complement activity, has been successfully used in aHUS.

Objectives: To optimize eculizumab therapy in aHUS patients by monitoring complement functional tests and markers of disease activity.

Patients/methods: We studied 18 patients with aHUS (10 males; eight females; age range, 2-40 years) treated with eculizumab to induce and/or maintain disease remission. Patients were followed up for a cumulative observation period of 160 months, during which blood samples were obtained at various time intervals to measure complement activity (Wieslab for the classical, alternative and mannose-binding lectin complement pathways) and the parameters of disease activity (haptoglobin and lactate dehydrogenase serum levels, and platelet count). The intravenous eculizumab doses of 12-33 mg kg(-1) were initially administered every week, with the interval between doses being gradually extended to 2 weeks, 3 weeks and 4 weeks on the basis of strict laboratory and clinical control.

Results: Complement activity was normal before eculizumab treatment, regardless of the state of the disease (activity or remission). It was completely suppressed 1 week, 2 weeks and 3 weeks after the last eculizumab infusion (mean values ± standard deviation: 1% ± 1% to 3% ± 5% for both the classical and alternative pathways; P = 0.0001 vs. baseline), and partially suppressed after 4 weeks (22% ± 26% and 16% ± 27%; P = 0.0001 vs. baseline). The increase in the time interval between eculizumab infusions did not change disease activity markers.

Conclusions: Monitoring complement tests can allow a safe reduction in the frequency of eculizumab administration in aHUS while keeping the disease in remission.

Keywords: atypical hemolytic uremic syndrome; complement; complement component 5; eculizumab; thrombotic microangiopathies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Atypical Hemolytic Uremic Syndrome / drug therapy*
  • Atypical Hemolytic Uremic Syndrome / genetics
  • Blood Platelets / metabolism
  • Child
  • Child, Preschool
  • Complement C3 / antagonists & inhibitors*
  • Complement C3 / chemistry
  • Complement C5 / antagonists & inhibitors*
  • Complement C5 / chemistry
  • Complement Factor H / chemistry
  • Female
  • Hemolysis
  • Humans
  • Kidney Transplantation
  • Male
  • Mutation
  • Platelet Count
  • Remission Induction
  • Thrombotic Microangiopathies / drug therapy
  • Time Factors
  • Young Adult


  • Antibodies, Monoclonal, Humanized
  • Complement C3
  • Complement C5
  • Complement Factor H
  • eculizumab