title: Albuminuria increases cystatin C excretion: implications for urinary biomarkers.
abstract: BACKGROUND
  Low-molecular weight (LMW) proteins, including albumin and novel urinary biomarkers of acute kidney injury (AKI) such as cystatin C and neutrophil gelatinase-associated lipocalin (NGAL), are normally absorbed from the glomerular filtrate by receptor-mediated transport. We evaluated the effect of albuminuria on urinary excretion of novel biomarkers.
  
  
  METHODS
  Sprague-Dawley rats given four injections over 2 days of 5 mg/g body wt/day bovine serum albumin (BSA) in saline were compared with controls given saline alone. Urinary cystatin C, albumin and protein excretion rates were compared prior to treatment (Day -1), after treatment (Day 2) and 4 days later (Day 6). A preliminary assessment of the clinical effect of proteinuria on the filtered urinary biomarkers cystatin C and NGAL was made by comparison with the effect on urinary interleukin-18 (IL-18) that is not absorbed from the glomerular filtrate, in a cohort of intensive care unit patients.
  
  
  RESULTS
  BSA induced transient increases in albuminuria, proteinuria and cystatinuria (P < 0.01, P < 0.001 and P < 0.001, respectively). Beyond a threshold 6-fold increase in albuminuria, cystatin C absorption was reduced by competitive inhibition. The excretion rates of all analytes returned to preinjection levels by Day 6. Clinical proteinuria was associated with increasing cystatin C and NGAL concentrations (n = 90, P < 0.0001) but not IL-18 (P = 0.12).
  
  
  CONCLUSIONS
  Proteinuria may increase the threshold for detection of AKI by increasing the excretion of LMW protein biomarkers.
authors.affiliation: Christchurch Kidney Research Group, Department of Medicine, University of Otago, Christchurch, New Zealand.
authors.forename: Maryam
authors.initials: M
authors.lastname: Nejat
authors.forename: Jonathan V
authors.initials: JV
authors.lastname: Hill
authors.forename: John W
authors.initials: JW
authors.lastname: Pickering
authors.forename: Charles L
authors.initials: CL
authors.lastname: Edelstein
authors.forename: Prasad
authors.initials: P
authors.lastname: Devarajan
authors.forename: Zoltán H
authors.initials: ZH
authors.lastname: Endre
mesh_terms: D058186:Acute Kidney Injury / Q000150:complications / Q000175:diagnosis / Q000652:urine*; D000209:Acute-Phase Proteins / Q000652:urine*; D000419:Albuminuria / Q000175:diagnosis / Q000209:etiology / Q000652:urine*; D000818:Animals; D015415:Biomarkers / Q000652:urine*; D002417:Cattle; D055316:Cystatin C / Q000652:urine*; D005260:Female; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine*; D008297:Male; D011518:Proto-Oncogene Proteins / Q000652:urine*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012710:Serum Albumin, Bovine / Q000008:administration & dosage
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D055316:Cystatin C; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D012710:Serum Albumin, Bovine