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Updated: Oct 29, 2025

Urinary Tract Infection in a Small Animal Model: Transurethral Catheterization of Male and Female Mice
Published on: December 1, 2017
Biomarkers for febrile urinary tract infection in children
Nader Shaikh1, Hui Liu2, Marcia Kurs-Lasky2
1Division 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@chp.edu.
Insights
New urinary biomarkers, including Neutrophil Gelatinase-Associated Lipocalin (NGAL), CCL3, and Interleukin-8 (IL-8), show promise for accurately diagnosing urinary tract infections (UTIs) in children.
Area of Science:
- Pediatric infectious diseases
- Clinical diagnostics
- Biomarker discovery
Background:
- Leukocyte esterase testing for urinary tract infection (UTI) diagnosis has suboptimal sensitivity and specificity.
- Recent research suggests novel protein markers may improve UTI diagnosis accuracy in children.
Purpose of the Study:
- To evaluate the diagnostic accuracy of specific urinary protein markers, including NGAL, CCL3, and IL-8, for identifying UTIs in children.
- To compare these markers against traditional diagnostic methods.
Main Methods:
- A prospective cross-sectional study involving 192 children.
- Urine samples were analyzed from febrile children with UTI, febrile controls without UTI, and healthy asymptomatic controls.
- Quantification of inflammatory proteins: CCL3, IL-8, CXCL1, TNF-alpha, IL-6, IFN-gamma, IL-17, IL-9, IL-2, and NGAL.
Main Results:
- Urinary NGAL, CCL3, and IL-8 levels were significantly higher in children with febrile UTI compared to controls.
- NGAL demonstrated a local bacteriostatic role via iron chelation.
- CCL3 and IL-8 are involved in leukocyte and neutrophil recruitment, respectively.
- These proteins were largely undetectable in asymptomatic children.
Conclusions:
- NGAL, CCL3, and IL-8 show potential as accurate biomarkers for the early diagnosis of pediatric UTIs.
- These markers may offer improved diagnostic capabilities over current methods.
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) A higher resolution version of the Graphical abstract is available as Supplementary information.
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