| Abstract: |
Background: Recurrent urinary tract infection (rUTI) is a major diagnostic and clinical challenge. Dysregulated innate immune responses, including antimicrobial peptides and cytokines, may underlie UTI susceptibility. This study investigates whether urinary concentrations of antimicrobial peptides and cytokines differ in children and adolescents with a history of rUTI and whether they can accurately classify rUTI status. Methods: In this single-center cross-sectional study, urine samples were collected from asymptomatic girls and adolescent females with a history of rUTI and age-matched controls recruited at Nationwide Children's Hospital (Columbus, Ohio, USA). Concentrations of antimicrobial peptides (alpha-defensins 1-3, beta-defensin 1, cathelicidin, secretory leukocyte protease inhibitor, lipocalin 2, and ribonuclease 7) and cytokines (interleukin-1 beta, interleukin-6, interleukin-8, and tumor necrosis factor alpha) were quantified using enzyme-linked immunosorbent assays. A logistic regression model with variable selection was developed to classify rUTI participants based on urinary biomarkers and clinical factors. Findings: Between 2019 and 2022, urine samples were analyzed from 42 participants with rUTI and 37 healthy controls without UTI. Compared to controls, participants with rUTI had lower concentrations of beta-defensin 1, cathelicidin, and ribonuclease 7, and higher concentrations of alpha-defensins 1-3, lipocalin 2, and secretory leukocyte protease inhibitor. Cytokine concentrations, including interleukin-1 beta, interleukin-6, interleukin-8, and tumor necrosis factor alpha, were elevated in the rUTI group. A multivariable classification model integrating urinary biomarkers with clinical features demonstrated high discriminatory performance with an area under the receiver operating curve of 0.97 and a prevalence-adjusted area under the precision-recall curve of 0.94. Interpretation: Girls and adolescent females with rUTI exhibit a distinct urinary immune profile characterized by dysregulated antimicrobial peptides and elevated proinflammatory cytokines. A model integrating these biomarkers with clinical features accurately classified rUTI status, supporting their potential utility as biomarkers for identifying youth with rUTI. [ABSTRACT FROM AUTHOR] |