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Biomarkers for febrile urinary tract infection in children

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Abstract

Background

The sensitivity and specificity of the leukocyte esterase test for the diagnosis of urinary tract infection (UTI) are suboptimal. Recent studies have identified markers that appear to more accurately differentiate children with and without UTI. The objective of this study was to determine the accuracy of these markers, which included CCL3, IL-8, CXCL1, TNF-alpha, IL-6, IFN-gamma, IL-17, IL-9, IL-2, and NGAL, in the diagnosis of UTI.

Methods

This was a prospective cross-sectional study to compare inflammatory proteins between urine samples from febrile children with a UTI, matched febrile controls without a UTI, and asymptomatic healthy controls.

Results

We included 192 children (75 with febrile UTI, 69 febrile controls, and 48 asymptomatic healthy controls). Urinary proteins that best discriminated between febrile children with and without UTI were NGAL, a protein that exerts a local bacteriostatic role in the urinary tract through iron chelation; CCL3, a chemokine involved in leukocyte recruitment; and IL-8, a cytokine involved in neutrophil recruitment. Levels of these proteins were generally undetectable in asymptomatic healthy children.

Conclusions

NGAL, CCL3, and IL-8 may be useful in the early diagnosis of UTI.

Trial registration

ClinicalTrials.gov (NCT01391793)

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Data availability

Data is available upon request.

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Code availability

Code is available upon request.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK; R01DK087870)

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Authors and Affiliations

  1. Division of General Academic Pediatrics, Children’s Hospital of Pittsburgh of UPMC, University of Pittsburgh School of Medicine, One Children’s Hospital Drive, 4401 Penn Ave, Pittsburgh, PA, 15224, USA

    Nader Shaikh, Hui Liu, Marcia Kurs-Lasky & Catherine S Forster

Authors
  1. Nader Shaikh
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  2. Hui Liu
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  3. Marcia Kurs-Lasky
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  4. Catherine S Forster
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Contributions

Dr. Shaikh conceptualized and designed the study, collected data, interpreted the data, drafted the initial manuscript, and reviewed and revised the manuscript. Dr. Forster interpreted the data and revised the manuscript. Hui Liu performed the initial statistical analysis and reviewed and revised the manuscript. Marcia Kurs-Lasky verified the statistical analysis and reviewed and revised the manuscript. All authors gave final approval of the version to be published and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Nader Shaikh.

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Ethics approval

The study was approved by the IRBs of the respective institution.

Consent to participate

All patients were consented prior to enrollment.

Conflict of interest

The authors declare no competing interests.

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Shaikh, N., Liu, H., Kurs-Lasky, M. et al. Biomarkers for febrile urinary tract infection in children. Pediatr Nephrol 37, 171–177 (2022). https://doi.org/10.1007/s00467-021-05173-x

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  • DOI: https://doi.org/10.1007/s00467-021-05173-x

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