Biomarkers for febrile urinary tract infection in children

• Published in: Pediatric nephrology (Berlin, West) Vol. 37; no. 1; pp. 171 - 177
• Main Authors: Shaikh, Nader, Liu, Hui, Kurs-Lasky, Marcia, Forster, Catherine S
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 2022; Springer; Springer Nature B.V
• Subjects: Analysis; Asymptomatic; Biological markers; Biomarkers - urine; Case-Control Studies; CCL3 protein; Chelation; Chemokine CCL3 - urine; Chemokines; Child; Children; Cross-Sectional Studies; Demographic aspects; Diagnosis; Diseases; Esterase; Fever - urine; Humans; Inflammation; Interleukin 17; Interleukin 2; Interleukin 6; Interleukin 8; Interleukin 9; Interleukin-8 - urine; Leukocyte migration; Leukocytes (neutrophilic); Lipocalin-2 - urine; Medical diagnosis; Medicine; Medicine & Public Health; Nephrology; Original Article; Pediatrics; Prospective Studies; Proteins; Risk factors; Tumor necrosis factor; Urinary tract; Urinary tract diseases; Urinary tract infections; Urinary Tract Infections - diagnosis; Urinary Tract Infections - urine; Urinary tract infections in children; Urogenital system; Urology; γ-Interferon; United States; Infectious disease; Biomarker; UTI; Diagnostic accuracy
• ISSN: 0931-041X; 1432-198X
• DOI: 10.1007/s00467-021-05173-x

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)
Graphical abstract
A higher resolution version of the Graphical abstract is available as Supplementary information