title: Neutrophil gelatinase-associated lipocalin: a novel marker of contrast nephropathy risk.
abstract: BACKGROUND
  Neutrophil gelatinase-associated lipocalin (NGAL, siderocalin) is a protein secreted by the kidney in the setting of acute kidney injury in an attempt to regulate and bind the release of catalytic iron from injured cells. We sought to evaluate the relationships between baseline NGAL, renal filtration function, and the degree of injury reflected by further increases in NGAL.
  
  
  METHODS
  This study was a prospective, blinded assessment of blood samples taken from patients with estimated glomerular filtration rate (eGFR) <75 ml/min/1.73 m(2) undergoing non-urgent coronary angiography and intervention using iodinated contrast. Renal transplant recipients, dialysis patients, and administration of iodinated contrast in the prior 30 days were exclusion criteria. Plasma NGAL was measured using the Alere™ assay. Serum creatinine (Cr) was measured using calibrated methods at a core laboratory. Samples were obtained at baseline, 1, 2, 4, 6, 12, 24, and 48 h after contrast administration.
  
  
  RESULTS
  A total of 63 subjects were enrolled with a mean age of 69.4 ± 9.1 years, 73% male, 35% with diabetes, and a mean eGFR of 47.82 ± 15.46 ml/min/1.73 m(2). The correlation between eGFR and NGAL was r = -0.61, 95% CI -0.74 to -0.44, p < 0.001. When stratified by baseline NGAL tertile, the peak NGAL observed for each group occurred at 29.0 ± 22.2 h and there was a twofold increase in the mean and peak change in NGAL across the tertiles. NGAL began to rise 6 h after contrast exposure and followed a similar course to serum Cr and at 48 h the overall mean NGAL was still rising. Only 2 patients sustained a rise in Cr of >25% or ≥0.5 mg/dl. Multivariate regression revealed that baseline NGAL (p < 0.001) and not eGFR (p = 0.95) was independently associated with the NGAL value at 48 h.
  
  
  CONCLUSIONS
  Baseline NGAL is strongly correlated with eGFR in patients with reduced renal filtration function undergoing coronary angiography. The magnitude of rise in NGAL is positively associated with the baseline value and is analogous to the time course of Cr in blood after contrast exposure. NGAL and not eGFR is an independent predictor of changes in the post-procedure NGAL. A baseline NGAL level is necessary for the interpretation of NGAL levels in the evaluation of acute kidney injury.
authors.affiliation: Section of Cardiology, Department of Medicine, Providence Hospital and Medical Center, St. John Providence Health System, Southfield, William Beaumont Hospital, Royal Oak, and Northern Michigan Hospital, Petoskey, MI 48374, USA. peteramccullough@gmail.com
authors.forename: Peter A
authors.initials: PA
authors.lastname: McCullough
authors.forename: Frances J
authors.initials: FJ
authors.lastname: Williams
authors.forename: David N
authors.initials: DN
authors.lastname: Stivers
authors.forename: Louis
authors.initials: L
authors.lastname: Cannon
authors.forename: Simon
authors.initials: S
authors.lastname: Dixon
authors.forename: Patrick
authors.initials: P
authors.lastname: Alexander
authors.forename: Danielle
authors.initials: D
authors.lastname: Runyan
authors.forename: Shukri
authors.initials: S
authors.lastname: David
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood* / Q000139:chemically induced / Q000175:diagnosis; D000209:Acute-Phase Proteins; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D003287:Contrast Media / Q000009:adverse effects*; D017023:Coronary Angiography / Q000009:adverse effects; D003404:Creatinine / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D017613:Iodine Compounds / Q000009:adverse effects; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011518:Proto-Oncogene Proteins / Q000097:blood*; D012044:Regression Analysis; D016037:Single-Blind Method; D018709:Statistics, Nonparametric
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D003287:Contrast Media; D017613:Iodine Compounds; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D003404:Creatinine