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Hemoglobinuria for the early identification of STEC-HUS in high-risk children: data from the ItalKid-HUS Network

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Abstract

Hemolytic uremic syndrome (HUS) represents one of the main causes of severe acute kidney injury in children. The most frequent form of HUS is caused by Shiga toxin-2 (Stx2)-producing Escherichia coli. Hemoglobinuria and hematuria are markers of glomerular damage, but their use has never been validated in HUS. We retrospectively analyzed the presence of hemoglobinuria/urinary red blood cells (RBCs) in children with Stx2-positive bloody diarrhea (BD) or with already ongoing STEC-HUS with the aim of validating its role in early identifying HUS. We reviewed all the pediatric patients with Stx2+ BD (group 1) and with ongoing HUS (group 2) referred to our center from 2010 to 2019. A total of 100 children were eligible for the study. In group 1, 22 patients showed hemoglobinuria/hematuria, while 41 remained negative. In 15/22 positive patients (68.2%), blood tests ruled in HUS, while in 7 (31.8%), HUS was excluded. Among the 41 patients persistently negative for hemoglobinuria/hematuria, no one developed HUS. The 37 STEC-HUS children (group 2) all had hemoglobinuria/RBCs at admission.

Conclusion: Hemoglobinuria/hematuria for the diagnosis of HUS in children with Stx2+ BD showed a sensitivity of 100% and a specificity of 85%. We strongly recommend patients with BD carrying Stx2 in stools to be closely monitored with urine dipstick/urinalysis to early identify HUS.

What is Known

• Children with bloody diarrhea secondary to Shiga toxin 2 are at high risk of hemolytic uremic syndrome, thus have to be carefully monitored for the development of the disease, in order to early be hospitalized and treated.

What is New

• Urine dipstick for hemoglobinuria can be used as an easy, inexpensive, and repeatable tool to early diagnose children with bloody diarrhea secondary to Shiga toxin 2 to have developed hemolytic uremic syndrome, with no risk of false-negative results.

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Data Availability

All data included in the study are stored and available for consultation.

Code availability

Not applicable.

Abbreviations

BD:

Bloody diarrhea

HUS:

Hemolytic uremic syndrome

IQR:

Interquartile range

LR+:

Positive likelihood ratio

LR−:

Negative likelihood ratio

NPV:

Negative predictive values

PPV:

Positive predictive values

STEC:

Shiga toxin-producing Escherichia coli

Stx:

Shiga toxin

TMA:

Thrombotic microangiopathy

95% CI:

95% confidence interval

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Acknowledgements

We want to acknowledge all the Pediatric Centers members of the ItalKid-HUS Network. We are also thankful to “PROGETTO ALICE ONLUS. ASSOCIAZIONE PER LA LOTTA ALLA SEU” for its continuous and precious support.

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Authors and Affiliations

  1. Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, via della Commenda 9, Milano, Italy

    Valentina Capone, Maria Cristina Mancuso, Giacomo Tamburini, Giovanni Montini & Gianluigi Ardissino

  2. Department of Clinical Sciences and Community Health, University of Milan, Milano, Italy

    Giovanni Montini

Authors
  1. Valentina Capone
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  2. Maria Cristina Mancuso
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  3. Giacomo Tamburini
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  4. Giovanni Montini
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  5. Gianluigi Ardissino
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Contributions

VC conceptualized and designed the study, drafted the initial manuscript and reviewed and revised the manuscript. MCM and GT supervised data collection and interpretation, reviewed and revised the manuscript. GM and GLA critically reviewed and revised the manuscript for important intellectual content. All authors approved the final manuscripts as submitted and agreed to be accountable for all the aspects of the work.

Corresponding author

Correspondence to Valentina Capone.

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Ethics approval for a retrospective study has been approved by local Ethics committee.

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Informed consent was obtained from all individual participants included in the study.

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Informed consent for publication was obtained from all individual participants included in the study.

Competing interests

The authors declare no competing interests.

Additional information

Communicated by Piet Leroy

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Capone, V., Mancuso, M.C., Tamburini, G. et al. Hemoglobinuria for the early identification of STEC-HUS in high-risk children: data from the ItalKid-HUS Network. Eur J Pediatr 180, 2791–2795 (2021). https://doi.org/10.1007/s00431-021-04016-z

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  • DOI: https://doi.org/10.1007/s00431-021-04016-z

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