Abstract
Background:
Pediatricians frequently use urinalysis to diagnose urinary tract infection (UTI) while awaiting urine culture results, but sensitivity and specificity of urinalysis are limited. This study evaluated the diagnostic accuracy of the antimicrobial peptides (AMPs) human α-defensin 5 (HD5) and human neutrophil peptides (HNP) 1–3 as novel UTI biomarkers in children.
Methods:
We prospectively enrolled 199 pediatric Emergency Department or Urgent Care patients evaluated for a UTI. Urine concentrations of HD5 and HNP1–3 were measured by enzyme-linked immunosorbent assay. Urine culture was the reference standard. Sensitivities and specificities of leukocyte esterase (LE), HD5, HNP1–3, and test combinations were compared.
Results:
For predicting positive urine culture, the areas under the receiver-operating characteristic curves for HD5 and HNP1–3 were 0.86 (95% confidence interval (CI): 0.81–0.92) and 0.88 (95% CI: 0.82–0.93), respectively. Compared to LE ≥ trace, the combination test “LE and HD5” increased specificity by 6% (95% CI: 3–10%) without decreasing sensitivity. In the subgroup whose urine was collected by a clean-catch method, combination tests “LE and HD5” and “HD5 and HNP1-3” increased specificity by > 10% compared to LE alone.
Conclusion:
Urine AMP profiles are a promising novel strategy as an adjunct to urinalysis to aid UTI diagnosis in children.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Copp HL, Shapiro DJ, Hersh AL. National ambulatory antibiotic prescribing patterns for pediatric urinary tract infection, 1998-2007. Pediatrics 2011;127:1027–33.
Freedman AL ; Urologic Diseases in America Project. Urologic diseases in North America Project: trends in resource utilization for urinary tract infections in children. J Urol 2005;173:949–54.
Spencer JD, Schwaderer A, McHugh K, Hains DS. Pediatric urinary tract infections: an analysis of hospitalizations, charges, and costs in the USA. Pediatr Nephrol 2010;25:2469–75.
Shaikh N, Morone NE, Lopez J, et al. Does this child have a urinary tract infection? JAMA 2007;298:2895–904.
Downs SM. Technical report: urinary tract infections in febrile infants and young children. The Urinary Tract Subcommittee of the American Academy of Pediatrics Committee on Quality Improvement. Pediatrics 1999;103:e54.
Kazi BA, Buffone GJ, Revell PA, Chandramohan L, Dowlin MD, Cruz AT. Performance characteristics of urinalyses for the diagnosis of pediatric urinary tract infection. Am J Emerg Med 2013;31:1405–7.
Williams GJ, Macaskill P, Chan SF, Turner RM, Hodson E, Craig JC. Absolute and relative accuracy of rapid urine tests for urinary tract infection in children: a meta-analysis. Lancet Infect Dis 2010;10:240–50.
Gorelick MH, Shaw KN. Screening tests for urinary tract infection in children: a meta-analysis. Pediatrics 1999;104:e54.
Spencer JD, Schwaderer AL, Becknell B, Watson J, Hains DS. The innate immune response during urinary tract infection and pyelonephritis. Pediatr Nephrol 2014;29:1139–49.
Jones DE, Bevins CL. Paneth cells of the human small intestine express an antimicrobial peptide gene. J Biol Chem 1992;267:23216–25.
Quayle AJ, Porter EM, Nussbaum AA, et al. Gene expression, immunolocalization, and secretion of human defensin-5 in human female reproductive tract. Am J Pathol 1998;152:1247–58.
Spencer JD, Hains DS, Porter E, et al. Human alpha defensin 5 expression in the human kidney and urinary tract. PLoS One 2012;7:e31712.
Ihi T, Nakazato M, Mukae H, Matsukura S. Elevated concentrations of human neutrophil peptides in plasma, blood, and body fluids from patients with infections. Clin Infect Dis 1997;25:1134–40.
Tikhonov I, Rebenok A, Chyzh A. A study of interleukin-8 and defensins in urine and plasma of patients with pyelonephritis and glomerulonephritis. Nephrol Dial Transplant 1997;12:2557–61.
Dieter RS. Sterile pyuria: a differential diagnosis. Compr Ther 2000;26:150–2.
Mori R, Yonemoto N, Fitzgerald A, Tullus K, Verrier-Jones K, Lakhanpaul M. Diagnostic performance of urine dipstick testing in children with suspected UTI: a systematic review of relationship with age and comparison with microscopy. Acta Paediatr 2010;99:581–4.
Whiting P, Westwood M, Watt I, Cooper J, Kleijnen J. Rapid tests and urine sampling techniques for the diagnosis of urinary tract infection (UTI) in children under five years: a systematic review. BMC Pediatr 2005;5:4.
Ray P, Le Manach Y, Riou B, Houle TT. Statistical evaluation of a biomarker. Anesthesiology 2010;112:1023–40.
Shaw KN, Hexter D, McGowan KL, Schwartz JS. Clinical evaluation of a rapid screening test for urinary tract infections in children. J Pediatr 1991;118:733–6.
Lachs MS, Nachamkin I, Edelstein PH, Goldman J, Feinstein AR, Schwartz JS. Spectrum bias in the evaluation of diagnostic tests: lessons from the rapid dipstick test for urinary tract infection. Ann Intern Med 1992;117:135–40.
Hoberman A, Wald ER, Reynolds EA, Penchansky L, Charron M. Pyuria and bacteriuria in urine specimens obtained by catheter from young children with fever. J Pediatr 1994;124:513–9.
Pryles CV, Steg NL. Specimens of urine obtained from young girls by catheter versus voiding; a comparative study of bacterial cultures, gram stains and bacterial counts in paired specimens. Pediatrics 1959;23:441–52.
Roberts KB, Subcommittee on Urinary Tract Infection, Steering Committee on Quality Improvement and Management. Urinary tract infection: clinical practice guideline for the diagnosis and management of the initial UTI in febrile infants and children 2 to 24 months. Pediatrics 2011;128:595–610.
Spencer JD, Schwaderer AL, Dirosario JD, et al. Ribonuclease 7 is a potent antimicrobial peptide within the human urinary tract. Kidney Int 2011;80:174–80.
Coady K, Marino T, Thomas J, Sosinski L, Neal B, Hammond L. An evaluation of 2,4-dichlorophenoxyacetic acid in the Amphibian Metamorphosis Assay and the Fish Short-Term Reproduction Assay. Ecotoxicol Environ Saf 2013;90:143–50.
Connor RJ. Sample size for testing differences in proportions for the paired-sample design. Biometrics 1987;43:207–11.
Acknowledgements
The authors thank the Nationwide Children’s Hospital Emergency Department Research Coordinators for enrolling patients in the study and collecting urine samples, and Evan Barr-Beare, Research Assistant at Nationwide Children’s Hospital, for assisting with the urine biorepository management.
This study was presented in part as a platform presentation at the Pediatric Academic Societies’ Meeting, 30 April–3 May 2015, San Diego, CA.
Author information
Authors and Affiliations
Corresponding author
Supplementary information
Supplementary Figure
(TIFF 1027 kb)
Supplementary Tables
(DOC 151 kb)
PowerPoint slides
Rights and permissions
About this article
Cite this article
Watson, J., Hains, D., Cohen, D. et al. Evaluation of novel urinary tract infection biomarkers in children. Pediatr Res 79, 934–939 (2016). https://doi.org/10.1038/pr.2016.33
Received:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/pr.2016.33
This article is cited by
-
Concentration of novel urinary tract infection biomarkers in neonates
Scientific Reports (2024)
-
Novel urine biomarkers to distinguish UTI from culture-negative pyuria
Pediatric Nephrology (2022)
-
Diagnostic value of biomarkers for paediatric urinary tract infections in primary care: systematic review and meta-analysis
BMC Family Practice (2021)
-
Evaluation of Antimicrobial Peptides at the Diagnosis of Urinary Tract Infection in Children
International Journal of Peptide Research and Therapeutics (2021)
-
Biomarkers that differentiate false positive urinalyses from true urinary tract infection
Pediatric Nephrology (2020)
