Neutrophil gelatinase-associated lipocalin (NGAL) in inflammatory bowel disease: association with pathophysiology of inflammation, established markers, and disease activity

J Gastroenterol. 2012 May;47(5):519-30. doi: 10.1007/s00535-011-0516-5. Epub 2011 Dec 27.

Abstract

Background: Neutrophil gelatinase-associated lipocalin (NGAL) is a multi-potent 25-kDa protein mainly secreted by neutrophils. In inflammatory bowel disease (IBD), overexpression of NGAL in colon epithelium has been previously shown. This is the first study analyzing serum and urinary NGAL levels in IBD patients, with regard to specific characteristics of patients and disease.

Methods: Serum and urinary NGAL levels were determined in 181 patients with IBD, 93 with ulcerative colitis (UC), and 88 with Crohn's disease (CD), 82 healthy controls (HC), and 41 patients with irritable bowel syndrome (IBS).

Results: Serum NGAL levels were elevated in IBD patients (88.19 ± 40.75 ng/mL) compared with either HC (60.06 ± 24.18 ng/mL) or IBS patients (60.80 ± 20.30 ng/mL), P < 0.0001. No significant difference was shown between UC (86.62 ± 35.40 ng/mL) and CD (89.92 ± 46.05 ng/mL). Significantly higher levels of serum NGAL were observed in patients with active (120.1 ± 38.46) versus inactive IBD (61.58 ± 15.98), P < 0.0001. Serum NGAL displayed a strong ability to distinguish active IBD from inactive disease, healthy controls, or IBS patients with a sensitivity of 100, 95, and 95% and a specificity of 68, 83, and 79%, respectively, performing better than erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in the assessment of disease activity in both UC and CD. Urinary NGAL levels showed neither significant difference among patients and controls nor correlation with disease activity.

Conclusions: Serum NGAL is elevated particularly in active IBD and correlates with established markers of inflammation and disease activity, implicating its role in the pathophysiology of IBD.

MeSH terms

  • Acute-Phase Proteins / physiology*
  • Acute-Phase Proteins / urine
  • Adolescent
  • Adult
  • Aged
  • Biomarkers / blood
  • Biomarkers / urine
  • C-Reactive Protein / metabolism
  • Case-Control Studies
  • Colitis, Ulcerative / diagnosis
  • Colitis, Ulcerative / metabolism
  • Colitis, Ulcerative / physiopathology
  • Crohn Disease / diagnosis
  • Crohn Disease / metabolism
  • Crohn Disease / physiopathology
  • Diagnosis, Differential
  • Female
  • Humans
  • Inflammatory Bowel Diseases / diagnosis
  • Inflammatory Bowel Diseases / metabolism
  • Inflammatory Bowel Diseases / physiopathology*
  • Irritable Bowel Syndrome / diagnosis
  • Irritable Bowel Syndrome / metabolism
  • Irritable Bowel Syndrome / physiopathology
  • Lipocalin-2
  • Lipocalins / blood
  • Lipocalins / physiology*
  • Lipocalins / urine
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins / blood
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins / urine
  • Sensitivity and Specificity
  • Severity of Illness Index
  • Young Adult

Substances

  • Acute-Phase Proteins
  • Biomarkers
  • LCN2 protein, human
  • Lipocalin-2
  • Lipocalins
  • Proto-Oncogene Proteins
  • C-Reactive Protein