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.
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Acute kidney injury
Atypical hemolytic uremic syndrome
the active subunit of Factor B with catalytic activity
Complement component 3
- D + HUS:
Diarrhea-associated hemolytic uremic syndrome
Glomerular filtration rate
Hemolytic uremic syndrome
Receiver operator curve
Renal replacement therapy
Serum complement membrane attack complex
Shiga-like toxin-producing Escherichia coli
Shiga toxin-associated hemolytic uremic syndrome
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The work was supported by the Grant Agency of Charles University (GAUK 194215).
The study was approved by a local research ethics board (REB). Informed consent was obtained from all subjects.
Conflict of interest
The authors declare that they have no conflicts of interest.
Communicated by Mario Bianchetti
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Karnisova, L., Hradsky, O., Blahova, K. et al. Complement activation is associated with more severe course of diarrhea-associated hemolytic uremic syndrome, a preliminary study. Eur J Pediatr 177, 1837–1844 (2018). https://doi.org/10.1007/s00431-018-3255-2
- Hemolytic uremic syndrome
- Shiga toxin-producing Escherichia coli
- Renal replacement therapy