Clinical and genetic predictors of atypical hemolytic uremic syndrome phenotype and outcome

Kidney Int. 2018 Aug;94(2):408-418. doi: 10.1016/j.kint.2018.02.029. Epub 2018 Jun 19.


Atypical hemolytic uremic syndrome (aHUS) is a rare, genetic, life-threatening disease. The Global aHUS Registry collects real-world data on the natural history of the disease. Here we characterize end-stage renal disease (ESRD)-free survival, the rate of thrombotic microangiopathy, organ involvement and the genetic background of 851 patients in the registry, prior to eculizumab treatment. A sex-specific difference was apparent according to age at initial disease onset as the ratio of males to females was 1.3:1 for childhood presentation and 1:2 for adult presentation. Complement Factor I and Membrane Cofactor Protein mutations were more common in patients with initial presentation as adults and children, respectively. Initial presentation in childhood significantly predicted ESRD risk (adjusted hazard ratio 0.55 [95% confidence interval 0.41-0.73], whereas sex, race, family history of aHUS, and time from initial presentation to diagnosis, did not. Patients with a Complement Factor H mutation had reduced ESRD-free survival, whereas Membrane Cofactor Protein mutation was associated with longer ESRD-free survival. Additionally extrarenal organ manifestations occur in 19%-38% of patients within six months of initial disease presentation (dependent on organ). Thus, our real-world results provide novel insights regarding phenotypic variables and genotypes on the clinical manifestation and progression of aHUS.

Keywords: complement; hemolytic uremic syndrome; thrombotic microangiopathy.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Atypical Hemolytic Uremic Syndrome / genetics
  • Atypical Hemolytic Uremic Syndrome / mortality*
  • Atypical Hemolytic Uremic Syndrome / pathology
  • Child
  • Complement Factor H / genetics
  • Complement Factor I / genetics
  • Disease Progression
  • Female
  • Humans
  • Kidney Failure, Chronic / epidemiology*
  • Kidney Failure, Chronic / pathology
  • Male
  • Membrane Cofactor Protein / genetics
  • Phenotype*
  • Prospective Studies
  • Registries / statistics & numerical data
  • Retrospective Studies
  • Sex Factors
  • Young Adult


  • CD46 protein, human
  • CFH protein, human
  • Membrane Cofactor Protein
  • Complement Factor H
  • CFI protein, human
  • Complement Factor I