Protein deficiency may be marker for recurrent UTIs

May 17, 2014

Local deficiency in neutrophil gelatinase-associated lipocalin may be a contributing pathogenic factor for recurrent urinary tract infections in some children, according to research from Boston Children’s Hospital reported at the AUA annual meeting in Orlando, FL.

Editor's note: This article has been updated since its original publication to include additional study data and commentary from the author/presenter.

Orlando, FL-Local deficiency in neutrophil gelatinase-associated lipocalin (NGAL) may be a contributing pathogenic factor for recurrent urinary tract infections (rUTIs) in some children, according to research from Boston Children’s Hospital reported at the AUA annual meeting in Orlando, FL.

Urinary NGAL concentration was evaluated in a case-control study that included 15 pediatric patients (ages 1 month to 18 years) seen for rUTI in the department of urology at Boston Children’s Hospital, and 15 children who presented to the emergency department who served as normal controls. The cases were selected based on having a history of at least two UTI episodes and absence of a current UTI or features predisposing them to UTI. Controls had no history of UTI or renal abnormalities and were not affected with any acute conditions associated with NGAL elevation.

Using immunoblotting, urinary NGAL was measurable in all of the rUTI patients. However, the mean NGAL concentration was significantly lower in the case group compared with the controls (21±10 ng/mL vs. 69±97 ng/mL). Similarly, the median NGAL concentration was also significantly lower among cases when compared with the controls (30 ng/mL vs. 60 ng/mL).

“NGAL is upregulated within the uroepithelium in patients with UTI, and it is a critical component of the innate immune system that exhibits bacteriostatic activity through iron sequestration. Therefore, we hypothesized that localized NGAL deficiency within the uroepithelium may contribute to the development of rUTI by increasing environmental iron that is required for bacterial growth,” said first author Catherine S. Forster, MD, a pediatrics resident at Boston Children’s Hospital.

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Further research needed to identify cause

“Our study provides proof of concept of an association between NGAL deficiency and rUTI, but the findings need to be verified in a larger population. Then, if the data are confirmed, further research would be warranted to determine the cause for the localized NGAL deficiency and implications for patient management.”

Senior author Richard S. Lee, MD, noted that establishing a role for NGAL deficiency in the pathogenesis of rUTIs could be important for reducing the burdens of evaluation and management for this patient population.

Dr. Lee“Identification of biologically based risk factors for rUTI might guide a tailored approach to the diagnostic workup and therapeutic intervention for these patients. If urinary NGAL can be used as a risk factor, perhaps we might find that serial measurements of urinary NGAL with a simple laboratory test could be used to monitor preventative treatment response,” said Dr. Lee, assistant professor of surgery (urology) at Harvard Medical School, Boston.

“We are very fortunate to have a well-documented and extensive patient and sample repository of patients with rUTI from our Voiding Improvement Clinic at Boston Children’s Hospital that will enable future longitudinal studies in this area.”

Whether NGAL deficiency would represent a target for intervention or would simply identify children who should receive counseling about behavioral or other pharmacologic or non-pharmacologic methods for reducing UTI risk would depend on the underlying cause for the low level. It may have a genetic basis or environmental factors might also play a considerable role in changes of urinary NGAL levels in rUTI.UT

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