Complement activation is associated with more severe course of diarrhea-associated hemolytic uremic syndrome, a preliminary study

Eur J Pediatr. 2018 Dec;177(12):1837-1844. doi: 10.1007/s00431-018-3255-2. Epub 2018 Sep 24.


Diarrhea-associated hemolytic uremic syndrome is characterized by hemolytic anemia, thrombocytopenia, and acute kidney injury secondary to enteric infection, typically Shiga toxin-producing Escherichia coli. Shiga toxin 2 is able to activate alternative complement pathways; therefore, the aim of the study was to analyze C3 as a predictor of clinical courses in patients with diarrhea-associated hemolytic uremic syndrome. We hypothesized that the patients with increased complement activation at admission suffered from a more severe course. We retrospectively analyzed data of 33 pediatric patients between 1999 and 2015 in the Czech Republic. We tested the association of a C3 concentration with biochemical parameters and the clinical data reflecting the severity of the disease. We found significant correlation between the initial C3 and the duration of renal replacement therapy (r = - 0.62, p = 0.0001) and the initial glomerular filtration rate (r = 0.36, p = 0.026). Patients with C3 < 0.825 g/L needed renal replacement therapy and also had significantly more renal complications (p = 0.015).Conclusion: Based on our study, decreased C3 concentrations can be used as one of the risk factors that can help predict the need for acute dialysis and a more severe course of disease in children with diarrhea-associated hemolytic uremic syndrome. What is Known: • Shiga toxin modulates the function of complement regulatory proteins and thus contributes to complement activation in patients with diarrhea-associated hemolytic uremic syndrome. • Risk factors that can predict the need for acute renal replacement therapy and poor outcome in patients with diarrhea-associated hemolytic uremic syndrome are mainly the combination of oligoanuria, dehydration, leukocytosis, high hematocrit > 23%, and neurological involvement. What is New: • A lowered concentration of C3 at the time of initial presentation of diarrhea-associated hemolytic uremic syndrome was associated with more severe renal failure and the need for renal replacement therapy along with the development of more extra renal complications. • Decreased C3 at admission can predict complicated course of diarrhea-associated hemolytic uremic syndrome.

Keywords: Complement; Hemolytic uremic syndrome; Renal replacement therapy; Shiga toxin-producing Escherichia coli.

MeSH terms

  • Biomarkers / blood
  • Child
  • Child, Preschool
  • Complement Activation / immunology*
  • Complement C3 / analysis*
  • Czech Republic
  • Diarrhea / complications
  • Diarrhea / immunology*
  • Female
  • Hemolytic-Uremic Syndrome / complications
  • Hemolytic-Uremic Syndrome / immunology*
  • Humans
  • Infant
  • Kidney / physiopathology
  • Male
  • Prognosis
  • ROC Curve
  • Renal Dialysis / statistics & numerical data
  • Retrospective Studies
  • Risk Factors


  • Biomarkers
  • Complement C3