Biomarkers that differentiate false positive urinalyses from true urinary tract infection

Pediatr Nephrol. 2020 Feb;35(2):321-329. doi: 10.1007/s00467-019-04403-7. Epub 2019 Nov 22.

Abstract

Background: The specificity of the leukocyte esterase test (87%) is suboptimal. The objective of this study was to identify more specific screening tests that could reduce the number of children who unnecessarily receive antimicrobials to treat a presumed urinary tract infection (UTI).

Methods: Prospective cross-sectional study to compare inflammatory proteins in blood and urine samples collected at the time of a presumptive diagnosis of UTI. We also evaluated serum RNA expression in a subset.

Results: We enrolled 200 children; of these, 89 were later demonstrated not to have a UTI based on the results of the urine culture obtained. Urinary proteins that best discriminated between children with UTI and no UTI were involved in T cell response proliferation (IL-9, IL-2), chemoattractants (CXCL12, CXCL1, CXCL8), the cytokine/interferon pathway (IL-13, IL-2, INFγ), or involved in innate immunity (NGAL). The predictive power (as measured by the area under the curve) of a combination of four urinary markers (IL-2, IL-9, IL-8, and NGAL) was 0.94. Genes in the pathways related to inflammation were also upregulated in serum of children with UTI.

Conclusions: Urinary proteins involved in the inflammatory response may be useful in identifying children with false positive results with current screening tests for UTI; this may reduce unnecessary treatment.

Keywords: Calculator; Diagnostic accuracy; Prediction rule; Risk; UTI.

MeSH terms

  • Biomarkers / blood*
  • Biomarkers / urine*
  • Child
  • Child, Preschool
  • False Positive Reactions
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Sensitivity and Specificity
  • Urinalysis
  • Urinary Tract Infections / blood*
  • Urinary Tract Infections / diagnosis*
  • Urinary Tract Infections / urine*

Substances

  • Biomarkers