title: Sensitivity and specificity of urinary neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 for the diagnosis of renal cell carcinoma.
abstract: OBJECTIVE
  Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) are urinary biomarkers of diagnostic relevance in a wide variety of acute and chronic kidney diseases. Their diagnostic sensitivity and specificity for kidney cancer are largely unknown and therefore the subject of this investigation.
  
  
  METHODS
  A prospective cohort study was performed to evaluate urine biomarkers for clear-cell and papillary subtypes of renal cancer (67 patients undergoing nephrectomy) and 55 control patients undergoing non-kidney surgery. Urinary KIM-1 and NGAL concentrations were determined by sensitive and specific ELISAs.
  
  
  RESULTS
  In renal cancer patients, median NGAL excretion was 0.52 (1st to 3rd quartiles: 0.28-0.82) ng/mg urinary creatinine (U(Cr)) before nephrectomy compared to 0.15 (0.04-0.31) ng/mg U(Cr) in controls (p < 0.001), and there was a modest decrease of 30% after nephrectomy (p < 0.008). NGAL was not correlated to tumor size (r = 0.19, p = 0.27) or stage. Before nephrectomy, KIM-1 excretion was 0.68 (0.40-1.12) ng/mg U(Cr) compared to 0.03 (0.01-0.06) in controls (p < 0.001). There was a linear correlation between KIM-1 excretion before nephrectomy and tumor size (Spearman's r = 0.66, p < 0.001), tumor stage, and a 50% decrease in median KIM-1 concentration 1 month following tumor excision (p < 0.01). Biomarker concentration ranges for renal cancer patients and controls overlapped substantially for NGAL but not KIM-1.
  
  
  CONCLUSIONS
  NGAL is not a sensitive or specific urinary biomarker of kidney cancer. Although KIM-1 had diagnostic sensitivity for kidney cancer, it is well known to reflect many types of kidney injuries, thus limiting its specificity as a diagnostic biomarker for renal cancer.
authors.affiliation: Department of Anesthesiology, Division of Clinical and Translational Research, Washington University in St. Louis, St. Louis, MO 63110-1093, USA. morrisse@wustl.edu
authors.forename: Jeremiah J
authors.initials: JJ
authors.lastname: Morrissey
authors.forename: Amy N
authors.initials: AN
authors.lastname: London
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Lambert
authors.forename: Evan D
authors.initials: ED
authors.lastname: Kharasch
mesh_terms: D000209:Acute-Phase Proteins / Q000652:urine*; D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000652:urine*; D005260:Female; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000652:urine*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine*; D008297:Male; D008562:Membrane Glycoproteins / Q000652:urine*; D008875:Middle Aged; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000652:urine*; D011991:Receptors, Virus; D012680:Sensitivity and Specificity
chemical_list: D000209:Acute-Phase Proteins; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D011991:Receptors, Virus