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Biomarkers that differentiate false positive urinalyses from true urinary tract infection
Nader Shaikh1,2, Judith M Martin3,4, Alejandro Hoberman3,4
1Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, USA. nader.shaikh@chp.edu.
Insights
New urinary protein markers show promise in accurately diagnosing urinary tract infections (UTIs) in children. This could reduce unnecessary antibiotic prescriptions by improving screening test specificity.
Area of Science:
- Pediatric infectious diseases
- Biomarker discovery
- Diagnostic accuracy
Background:
- The leukocyte esterase test for urinary tract infections (UTIs) has suboptimal specificity.
- Current screening methods lead to unnecessary antimicrobial use in children.
Purpose of the Study:
- To identify more specific screening tests for pediatric UTIs.
- To reduce the number of children receiving unnecessary antibiotic treatment.
Main Methods:
- Prospective cross-sectional study comparing inflammatory proteins in blood and urine.
- Evaluation of serum RNA expression in a subset of pediatric patients.
- Analysis of 200 children with presumptive UTI diagnoses.
Main Results:
- Urinary proteins like IL-9, IL-2, CXCL12, CXCL1, CXCL8, IL-13, INFγ, and NGAL differentiated children with and without UTI.
- A combination of IL-2, IL-9, IL-8, and NGAL achieved a predictive power (AUC) of 0.94.
- Inflammation-related genes were upregulated in the serum of children with UTI.
Conclusions:
- Urinary inflammatory proteins can aid in identifying false positive UTI screening results.
- Improved diagnostic accuracy may significantly reduce unnecessary antibiotic treatment in children.
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.
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