title: Urinalysis is more specific and urinary neutrophil gelatinase-associated lipocalin is more sensitive for early detection of acute kidney injury.
abstract: BACKGROUND
  Neutrophil gelatinase-associated lipocalin (NGAL) protein is a promising biomarker to detect acute kidney injury (AKI). Earlier detection of AKI could facilitate evaluation of novel therapeutic strategies.
  
  
  METHODS
  Random and 24-h urine samples were prospectively obtained from 125 normal volunteers for analytic validation of a urinary enzyme-linked immunosorbent assay for NGAL. For clinical validation of the test, urine from 363 emergency department patients admitted to the hospital was obtained for NGAL enzyme-linked immunosorbent assay and urinalysis and AKI was determined by the use of Acute Kidney Injury Network (AKIN) criteria.
  
  
  RESULTS
  NGAL was stable in urine for 7 days when ambient, 4 °C or frozen (-20 or -70 °C). The assay was linear between 0.24 and 10,000 ng/mL with a limit of quantitation of 0.24 ng/mL. Intra- and inter-assay precision were excellent (coefficient of variation <5%); however, urinary white blood cells were associated with increased NGAL levels. The 95th percentile reference value for NGAL in females is ≤ 65.0 and ≤ 23.4 ng/mL in males. Urinary NGAL levels increased with AKI stage but had only fair sensitivity (65%) and specificity (65%) to differentiate no AKI versus Stages 1, 2 or 3 (area under the curve 0.70). Urinalysis with microscopy was very specific (91%) but not very sensitive (22%) with an area under the curve of 0.57.
  
  
  CONCLUSIONS
  NGAL can be reliably measured in clinical urine samples, although pyuria is an important potential confounder. In our cohort, increased urinary NGAL was associated with AKI by the AKIN criteria; however, the sensitivity and specificity were only fair, in part because patients with pre-renal causes are not excluded by AKIN criteria. Conversely, findings on microscopic urinalysis are very specific for AKI.
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic Rochester, Rochester, MN, USA.
authors.forename: Carrie A
authors.initials: CA
authors.lastname: Schinstock
authors.forename: Merfake H
authors.initials: MH
authors.lastname: Semret
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Wagner
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Borland
authors.forename: Sandra C
authors.initials: SC
authors.lastname: Bryant
authors.forename: Kianoush B
authors.initials: KB
authors.lastname: Kashani
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Larson
authors.forename: John C
authors.initials: JC
authors.lastname: Lieske
mesh_terms: D058186:Acute Kidney Injury / Q000175:diagnosis* / Q000652:urine; D000209:Acute-Phase Proteins / Q000652:urine*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000652:urine*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000652:urine; D042241:Early Diagnosis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000652:urine*; D012680:Sensitivity and Specificity; D016482:Urinalysis; D055815:Young Adult
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D003404:Creatinine