Establishment of Baseline Urinary Antimicrobial Peptide Levels by Age: A Prospective Observational Study

Abstract Background Antimicrobial peptides (AMPs) are key effectors of urinary tract innate immunity. Identifying differences in urinary AMP levels between younger and older adults is important in understanding older adults’ susceptibility and response to urinary tract infections (UTI) and AMP use as diagnostic biomarkers. We hypothesized that uninfected older adults have higher urinary human neutrophil peptides 1-3 (HNP 1-3), human alpha-defensin-5 (HD-5), and human beta-defensin-2 (hBD-2), but lower urinary cathelicidin (LL-37) than younger adults. Methods We conducted a cross-sectional study of patients aged ≥18 years completing a family medicine clinic nonacute visit. Enzyme-linked immunosorbent assays were performed for AMPs. We identified associations between age and AMPs using unadjusted and multivariable linear regression models. Results Of the 308 subjects, 144 (46.8%) were ≥65 years of age. Comparing age ≥65 versus < 65 years, there were no significant differences in HNP 1-3 (p = .371), HD5 (p = .834), or LL-37 (p = .348) levels. Values for hBD-2 were lower in older adults versus younger (p < .001). In multivariable analyses, older males and females had significantly lower hBD-2 levels (p < .001 and p = .004). Models also showed urine leukocyte esterase was associated with increased levels of HNP 1-3 and HD5; hematuria with increased hBD-2; and urine cultures with contamination with increased HNP 1-3 and hBD-2. Conclusions Baseline urinary HNP 1-3, HD-5, and LL-37 did not vary with age. Older adults had lower baseline hBD-2. This finding has implications for the potential use of urinary AMPs as diagnostic markers and will facilitate further investigation into the role of innate immunity in UTI susceptibility in older adults.