Urinary Antimicrobial Peptides and Cytokines as Biomarkers for Recurrent Urinary Tract Infection in Children and Adolescents

Background: Recurrent urinary tract infection (rUTI) is a major diagnostic and management 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: Urine samples were collected from 42 girls and adolescent females with a history of rUTI and 37 matched healthy controls. 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. Results: 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. The predictive model demonstrated high accuracy, with an area under the receiver operating curve of 0.97 and a prevalence-adjusted area under the precision-recall curve of 0.94. Conclusions: Girls and adolescent females with rUTI exhibit a distinct urinary immune profile characterized by dysregulated antimicrobial peptides and elevated proinflammatory cytokines. A predictive model integrating these biomarkers with clinical features accurately classified rUTI status, supporting their potential utility as diagnostic tools for pediatric UTI.