Differentiating Asymptomatic Bacteriuria From Urinary Tract Infection in the Pediatric Neurogenic Bladder Population: NGAL As a Promising Biomarker

Abstract

Objective: To evaluate whether urinary antimicrobial peptides (AMPs) can discriminate between asymptomatic bacteriuria (ASB) and urinary tract infection (UTI) in pediatric patients with neurogenic bladder (NGB). Design/Methods: Bladder urine was collected from pediatric patients (≤18 years old) with NGB without augmentation cystoplasty. Patients were divided into the following groups based on symptomatology and results of urinalysis/urine culture: (a) UTI, (b) ASB, and (c) sterile. Urine AMPs β defense 1 (BD-1), neutrophil gelatinase-associated lipocalin (NGAL), cathelicidin (LL-37), hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein (HIP/PAP), and human α defensin 5 (HD-5) were compared between groups by enzyme-linked immunosorbent assays. In addition, urines from pediatric controls without NGB or UTI were also analyzed. Significance was determined using Student's t test for parametric or Mann-Whitney U test for nonparametric data. A p value of <.05 was considered significant. Results: Thirty-six patients with NGB from a spinal dysraphism were evaluated: UTI, n = 6; ASB, n = 18; sterile, n = 12. These groups did not differ significantly by age but did significantly differ by gender (p = .0139). NGAL significantly differed between UTI and ASB groups (median 38.5 ng/mg vs 15.5 ng/mg, respectively; p = .0197) with a sensitivity and specificity of 82.4% and 83.3%, respectively. HIP/PAP, BD-1, HD-5, LL-37, and NGAL levels were all significantly higher in sterile NGB urines compared to 17 non-NGB pediatric controls (p < .0001, p = .0020, p = .0035, p = .0006, and p = .0339, respectively). Conclusion: All five urinary AMPs evaluated were significantly elevated in NGB patients compared to controls. NGAL levels may help differentiate between UTI and ASB in pediatric NGB patients.

Keywords: NGAL; antimicrobial peptides; asymptomatic bacteriuria; myelomeningocele; spinal dysraphism; urinary tract infection.

Figure 1.

(A–E) Urinary antimicrobial peptide (AMP) levels (β defense 1 [BD-1], human α defensin 5 [HD-5], cathelicidin [LL-37], hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein [HIP/PAP], neutrophil gelatinase-associated lipocalin [NGAL]) in neurogenic bladder (NGB) group patients (Neurogenic) and non-NGB controls (Controls) on ELISA. # p = .0020. ## p = .0035. % p = .0006. %% p < .0001. *p = .0339. **p = .0197. (F) NGAL receiver operator characteristics (ROC) curve with area under the curve (AUC) between asymptomatic bacteriuria (ASB) and urinary tract infection (UTI) NGB patients.

Figure 2.

Urinary β defense 1 (BD-1) and hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein (HIP/PAP) ELISA levels between sterile urine from freely voiding neurogenic bladder (NGB) patients compared to non-NGB control patients. *p = .0127. **p = .0023.