title: Establishment of reference values for novel urinary biomarkers for renal damage in the healthy population: are age and gender an issue?
abstract: BACKGROUND
  Recently, a lot of research has focused on the discovery of novel renal biomarkers. Among others, the urinary kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) have been proven to be promising biomarkers in a wide variety of renal pathologies. However, little is known about the normal concentrations in urine of healthy subjects. Therefore, the goal of our study is to establish reference values for urinary KIM-1, NGAL, N-acetyl-β-D-glucosamidase (NAG), and cystatin C in a healthy population, taking into account possible effects of age and gender.
  
  
  METHODS
  We collected urine samples from 338 healthy, nonsmoking subjects between 0 and 95 years old. Subjects with elevated α1-microglobulin values were excluded. Next to the urinary concentrations of KIM-1, NGAL, NAG, and cystatin C, we measured urinary creatinine and specific gravity to correct for urinary dilution. The possible effect of age and gender on the four urinary biomarkers was investigated, and the reference values were established.
  
  
  RESULTS
  For the absolute urinary concentrations of the biomarkers, age had a significant effect on all the biomarkers, except for cystatin C, whereas gender significantly affected all four of them, except for NAG. The normalization of biomarkers for creatinine and specific gravity had an effect on the correlation between the biomarkers on one hand and age and gender on the other.
  
  
  CONCLUSIONS
  In conclusion, age and gender had different effects on KIM-1, NGAL, NAG, and cystatin C. Based on this knowledge, age- and gender-specific reference values for KIM-1, NGAL, NAG, and cystatin C were established.
authors: Valérie
authors: V
authors: Pennemans
authors: Jean-Michel
authors: JM
authors: Rigo
authors: Christel
authors: C
authors: Faes
authors: Carmen
authors: C
authors: Reynders
authors: Joris
authors: J
authors: Penders
authors: Quirine
authors: Q
authors: Swennen
mesh_terms: D000118:Acetylglucosaminidase / Q000652:urine*; D000209:Acute-Phase Proteins / Q000652:urine*; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000652:urine; D002648:Child; D002675:Child, Preschool; D055316:Cystatin C / Q000652:urine*; D005260:Female; D064368:Healthy Volunteers; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine*; D008297:Male; D008562:Membrane Glycoproteins / Q000652:urine*; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000652:urine*; D011991:Receptors, Virus; D012016:Reference Values; D051436:Renal Insufficiency, Chronic / Q000652:urine*; D012737:Sex Factors; D055815:Young Adult
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D055316:Cystatin C; 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; D000118:Acetylglucosaminidase