Urinary NGAL Deficiency in Recurrent Urinary Tract Infections

Abstract

Introduction

Children with recurrent urinary tract infections (rUTI) often do not have an identifiable cause of their infections. Neutrophil gelatinase-associated lipocalin (NGAL) is known to be upregulated within the uroepithelium and kidney of patients with UTI and exhibits a localized bacteriostatic effect through iron chelation. We hypothesize that some patients with rUTI without an identifiable cause of their recurrent infections are locally deficient for NGAL production.

Materials and Methods

Patients seen in the urology clinic for rUTI who were under 21 years of age were enrolled. Patients were excluded if they had UTI at the time of enrollment, evidence of renal disease, decreased renal function, known anatomic abnormality of the genitourinary tract or other reason that predisposes to UTI, such as requirement for intermittent catheterization, neurogenic bladder, or unrepaired posterior urethral valves. Control patients were healthy children enrolled from the emergency department, and were included if they no history of UTI or renal dysfunction, a normal urinalysis at the time of enrollment, and were not presenting with diagnosis associated with increased NGAL levels, such as acute kidney injury or infection. NGAL was measured by immunoblot.

Results

5 cases and controls were enrolled. Median urinary NGAL levels were significantly decreased in rUTI patients compared to controls (15 (14,29) ng/ml vs 30 (27,61) ng/ml, p=0.002). Although comparatively diminished, measurable NGAL levels were present in all patients with rUTI.

Discussion

Here, we explored the hypothesis that a lack of NGAL production may be a factor in the pathogenesis of rUTI. While there are several studies investigating the role of NGAL both in UTI and in iron trafficking within the genitourinary environment, there are no previous works that explore the concept of NGAL deficiency. There are several limitations to this study, mostly related to the exploratory nature of this investigation. The limitations of this study include the lack of matching between cases and controls, and the small number of patients in the cohorts.

Conclusions

Urinary NGAL is significantly decreased in patients with rUTI compared to patients without rUTI. These data suggest that some patients with rUTI may be predisposed to UTI because of a relative local deficiency in urinary NGAL production.