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


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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Fig. 1
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Fig. 3



Acute kidney injury


Atypical hemolytic uremic syndrome


Alternative pathway


the active subunit of Factor B with catalytic activity


Blood pressure


Complement component 3

D + HUS:

Diarrhea-associated hemolytic uremic syndrome


Estimated GFR


Glomerular filtration rate




Hemolytic uremic syndrome


Lactate dehydrogenase


Peritoneal dialysis


Receiver operator curve


Renal replacement therapy


Serum creatinine


Serum complement membrane attack complex


Shiga-like toxin-producing Escherichia coli


Shiga toxin-associated hemolytic uremic syndrome


Shiga toxin


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Research funding

The work was supported by the Grant Agency of Charles University (GAUK 194215).

Author information

Lucia Karnisova contributed to the study design, data collection, data analysis, and wrote the manuscript.

Jakub Zieg helped write the manuscript, contributed to coordination and preparation of the study, and data collection.

Ondrej Hradsky carried out a statistical and data analysis, participated in the preparation and design of the study, and helped write the manuscript.

Filip Fencl referred the case and was involved in writing the clinical history and critically reviewed the manuscript.

Kveta Blahova referred the case and was involved in writing the clinical history.

Tomas Zaoral referred the case and was involved in writing the clinical history.

Zdenek Dolezal referred the case and was involved in writing the clinical history.

All the authors reviewed, revised and approved the final manuscript.

Correspondence to Lucia Karnisova.

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Informed consent

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.

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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

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  • Complement
  • Hemolytic uremic syndrome
  • Shiga toxin-producing Escherichia coli
  • Renal replacement therapy