Biomarkers that differentiate false positive urinalyses from true urinary tract infection.
Nader Shaikh, Judith M Martin, Alejandro Hoberman, Megan Skae, Linette Milkovich, Christi McElheny, Robert W Hickey, Lucine V Gabriel, Diana H Kearney, Massoud Majd, Eglal Shalaby-Rana, George Tseng, Jay Kolls, William Horne, Zhiguang Huo, Timothy R Shope
Author Information
Nader Shaikh: Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, USA. nader.shaikh@chp.edu.
Judith M Martin: Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, USA.
Alejandro Hoberman: Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, USA.
Megan Skae: Division of General Academic Pediatrics, Children's Hospital of Pittsburgh of UPMC, One Children's Hospital Drive, 4401 Penn Ave, Pittsburgh, PA, 15224, USA.
Linette Milkovich: Division of General Academic Pediatrics, Children's Hospital of Pittsburgh of UPMC, One Children's Hospital Drive, 4401 Penn Ave, Pittsburgh, PA, 15224, USA.
Christi McElheny: Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Robert W Hickey: Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, USA.
Lucine V Gabriel: Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, USA.
Diana H Kearney: Division of General Academic Pediatrics, Children's Hospital of Pittsburgh of UPMC, One Children's Hospital Drive, 4401 Penn Ave, Pittsburgh, PA, 15224, USA.
Massoud Majd: Children's National Health System, Washington, USA.
Eglal Shalaby-Rana: Children's National Health System, Washington, USA.
George Tseng: Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
Jay Kolls: Tulane School of Medicine, New Orleans, PA, USA.
William Horne: Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, USA.
Zhiguang Huo: Department of Biostatistics, Biostatistics, College of Public Health & Health Professions and College of Medicine, University of Florida, Gainesville, USA.
Timothy R Shope: Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, USA.
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, INF��), 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.
