title: Urinary KIM-1, but not urinary cystatin C, should be corrected for urinary creatinine.
abstract: OBJECTIVE
  The interest for tubular damage markers such as urinary cystatin C (U-CystC) and kidney injury molecule-1 (U-KIM-1) grows, especially for the diagnosis of acute kidney injury. The trend to measure proteins in spot urine samples instead of 24-h urine collections calls for adjustment of urine dilution with urinary creatinine (UCr). However, it is not known whether UCr adjustment provides a more true value of basal U-CystC and U-KIM-1 levels than absolute values.
  
  
  METHODS
  This study examines the rationale for UCr correction for U-CystC and U-KIM-1 by exploring the linear relations between U-CystC and U-KIM-1 and UCr, respectively, and the biological day to day variation of absolute concentrations and UCr adjusted values of the two biomarkers.
  
  
  RESULTS
  Both U-CystC and U-KIM-1 concentrations correlated positively with UCr (R=0.37, P<0.001 and R=0.62, P<0.001, respectively) in 378 participants in a community cohort, which indicated a rationale for adjustment with UCr. However, U-CystC/Cr ratio associated negatively with UCr (R=- 0.31, P<0.001), which could indicate a certain amount of 'over-adjustment'. Morning urine collected for 10 consecutive days from 13 healthy volunteers showed a biological day to day variation of 82% for U-CystC, 75% for U-cystC/Cr ratio, 70% for U-KIM-1 and 46% for U-KIM-1/Cr ratio.
  
  
  CONCLUSIONS
  This study supports the use of U-KIM-1/Cr ratio in clinical population studies. Data supporting the use of U-CysC/U-Cr ratio were less convincing and the possible confounding of UCr has to be acknowledged in clinical settings.
authors.affiliation: Department of Medical Sciences, Uppsala University, Sweden. Electronic address: Johanna.Helmersson_Karlqvist@medsci.uu.se.
authors.forename: Johanna
authors.initials: J
authors.lastname: Helmersson-Karlqvist
authors.affiliation: Department of Medical Sciences, Uppsala University, Sweden; School of Health and Social Studies, Dalarna University, Falun, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Ärnlöv
authors.affiliation: School of Health and Social Studies, Dalarna University, Falun, Sweden; Centre for Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
authors.forename: Axel C
authors.initials: AC
authors.lastname: Carlsson
authors.affiliation: Department of Medical Sciences, Uppsala University, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Lind
authors.affiliation: Department of Medical Sciences, Uppsala University, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Larsson
mesh_terms: D000368:Aged; D015331:Cohort Studies; D003404:Creatinine / Q000652:urine*; D055316:Cystatin C / Q000652:urine*; D005260:Female; D000072596:Hepatitis A Virus Cellular Receptor 1 / Q000378:metabolism*; D006801:Humans; D008297:Male
chemical_list: D055316:Cystatin C; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D003404:Creatinine
keywords: Biological variation; Creatinine ratio; Cystatin C; Kidney injury molecule-1; Tubular biomarker