title: Urinary NGAL deficiency in recurrent urinary tract infections.
abstract: Children with recurrent urinary tract infections (rUTI) often show no 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 have locally deficient NGAL production. We therefore explored whether a lack of NGAL production may be a factor in the pathogenesis of rUTI.
  
  
  
  Patients seen in the urology clinic for rUTI who were <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 reasons that predispose to UTI, such as neurogenic bladder, the need for intermittent catheterization, or unrepaired posterior urethral valves. Control patients were healthy children enrolled from the emergency department with no history of UTI or renal dysfunction, normal urinalysis at the time of enrollment, and presenting no diagnosis associated with increased NGAL levels, such as acute kidney injury or infection. NGAL was measured by immunoblot.
  
  
  
  Fifteen cases and controls were enrolled. Median urinary NGAL levels were significantly decreased in rUTI patients compared with 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.
  
  
  
  Urinary NGAL is significantly decreased in patients with compared with 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.
authors.affiliation: Department of Medicine, Harvard Medical School and Boston Children's Hospital, Boston, MA, USA. Catherine.Forster@cchmc.org.|Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, MLC 9016, Cincinnati, OH, 45229, USA. Catherine.Forster@cchmc.org.
authors.forename: Catherine S
authors.initials: CS
authors.lastname: Forster
authors.affiliation: Department of Urology, Harvard Medical School and Boston Children's Hospital, Boston, MA, USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Johnson
authors.affiliation: Department of Urology, Harvard Medical School and Boston Children's Hospital, Boston, MA, USA.
authors.forename: Viral
authors.initials: V
authors.lastname: Patel
authors.affiliation: Department of Medicine, Columbia University, New York, NY, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Wax
authors.affiliation: Department of Medicine, Harvard Medical School and Boston Children's Hospital, Boston, MA, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Rodig
authors.affiliation: Department of Medicine, Columbia University, New York, NY, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Barasch
authors.affiliation: Department of Medicine, Harvard Medical School and Boston Children's Hospital, Boston, MA, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Bachur
authors.affiliation: Department of Urology, Harvard Medical School and Boston Children's Hospital, Boston, MA, USA.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000378:metabolism / Q000652:urine; D015153:Blotting, Western; D002648:Child; D002675:Child, Preschool; D004198:Disease Susceptibility / Q000378:metabolism / Q000652:urine; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D000071068:Lipocalin-2 / Q000378:metabolism / Q000652:urine*; D008297:Male; D011446:Prospective Studies; D012008:Recurrence; D015854:Up-Regulation; D014551:Urinary Tract / Q000378:metabolism*; D014552:Urinary Tract Infections / Q000209:etiology / Q000652:urine*; D019459:Urothelium / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C489506:LCN2 protein, human; D000071068:Lipocalin-2
keywords: Biomarker; Child; Immune systems disease; Lipocalin-2; Urinary tract infection