title: Cystatin C standardization decreases assay variation and improves assessment of glomerular filtration rate.
abstract: BACKGROUND
  Cystatin C is increasingly used in glomerular filtration rate (GFR) estimation equations. The dependence of cystatin C results upon the analytical method has been a major source of controversy.
  
  
  METHODS
  Cystatin C was measured with non-standardized turbidimetric Roche Generation 1 and standardized nephelometric Siemens assays in 3666 and additionally with standardized Roche Generation 2 and Siemens in 567 blood samples of the Berlin Initiative Study. Cystatin C-based GFR was assessed with CKD-EPIcys (Chronic Kidney Disease Epidemiology) and CAPA (Caucasian, Asian, Pediatric, Adult) equations and the impact of the assays on GFR estimation was determined. Equation performance compared to measured GFR was evaluated.
  
  
  RESULTS
  Concordance of Roche Gen2 and Siemens was high with median difference of 0.003 ± 0.13 mg/L (limits of agreement: -0.12 to 0.12) and Passing Bablok correlation was essentially perfect. Roche Gen1 assay showed worse concordance with Siemens: median difference was 0.08 ± 0.13 mg/L (limits of agreement: -0.18 to 0.34) and correlation was inferior. Mean difference (± SD) of estimated GFRCKD-EPIcys was 0 ± 4 mL/min/1.73 m(2) for Gen2 and Siemens compared to -5 ± 8 with Gen1. Performance of GFR estimating equations was not influenced by the choice of Siemens or Gen2 assays.
  
  
  CONCLUSIONS
  Standardization of Roche Gen2 assay improved accuracy of cystatin C measurement compared to Siemens. It suggests only negligible method bias and results in equal performance of both assays when estimating GFR indicating that successful calibration has led to major progress in cystatin C analysis.
authors.affiliation: Charité University Medicine, Institute of Public Health, Berlin, Germany. Electronic address: natalie.ebert@charite.de.
authors.forename: Natalie
authors.initials: N
authors.lastname: Ebert
authors.affiliation: Division of Nephrology, Centre Hospitalier Universitaire du Sart-Tilman, Liège, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Delanaye
authors.affiliation: San Francisco VA Medical Center, San Francisco, USA; University of California, San Francisco, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Shlipak
authors.affiliation: Institute of Biostatistics and Clinical Epidemiology, Charité, Berlin, Germany.
authors.forename: Olga
authors.initials: O
authors.lastname: Jakob
authors.affiliation: Institute of Clinical Epidemiology and Medical Biostatistics, University Tübingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Martus
authors.affiliation: Limbach Laboratory, Heidelberg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Bartel
authors.affiliation: Division of Nephrology, Charité University Medicine, Campus Mitte, Berlin, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Gaedeke
authors.affiliation: Division of Nephrology, Charité University Medicine, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: van der Giet
authors.affiliation: Division of Nephrology, Charité University Medicine, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Schuchardt
authors.affiliation: Department of Clinical Chemistry, Centre Hospitalier Universitaire du Sart-Tilman, Liège, Belgium.
authors.forename: Etienne
authors.initials: E
authors.lastname: Cavalier
authors.affiliation: Charité University Medicine, Institute of Public Health, Berlin, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Schaeffner
mesh_terms: D000368:Aged; D001774:Blood Chemical Analysis / Q000592:standards*; D055316:Cystatin C / Q000097:blood*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D012015:Reference Standards; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000503:physiopathology
chemical_list: D055316:Cystatin C
keywords: Assay standardization; Cystatin C; Glomerular filtration rate; Renal biomarkers