title: Analytic and clinical validation of a standardized cystatin C particle enhanced turbidimetric assay (PETIA) to estimate glomerular filtration rate.
abstract: BACKGROUND
  Cystatin C is an alternative biomarker for assessing glomerular filtration rate (GFR), yet lack of standardization could hinder its widespread use. In this study we analytically and clinically validated a newer cystatin C particle-enhanced turbidimetric assay (PETIA) traceable to a certified reference material and compared it to the more commonly used particle-enhanced nephelometric assay (PENIA).
  
  
  METHODS
  Samples from four patient cohorts at the Mayo Clinic were studied: 1) clinical convenience samples (n=50); 2) samples from patients undergoing iothalamate urinary clearance testing for clinical indications (n=101); 3) volunteers without kidney disease (n=292); 4) samples from 1999-2000 with previous cystatin C measurements.
  
  
  RESULTS
  The cystatin C PETIA was analytically robust between 0.15 mg/L and 8.36 mg/L. PETIA cystatin C values were 27.5% higher than PENIA results. Furthermore, PENIA results were 12.9% lower in 2010 than in 2000. PETIA cystatin C values and existing equations performed reasonably well to estimate GFR with an overall -7.4% bias for all patients analyzed. Age and gender specific reference intervals were established for the PETIA cystatin C.
  
  
  CONCLUSIONS
  Cystatin C can be precisely measured by PETIA traceable to the international reference material, ERM-DA471/IFCC, using a routine chemistry autoanalyzer. There are important biases between this assay and the widely employed Siemens PENIA. This study highlights the importance of assay standardization if cystatin C is to be widely used to estimate GFR.
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Nikolay V
authors.initials: NV
authors.lastname: Voskoboev
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Larson
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Rule
authors.forename: John C
authors.initials: JC
authors.lastname: Lieske
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D055316:Cystatin C / Q000097:blood* / Q000592:standards; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009391:Nephelometry and Turbidimetry / Q000592:standards*; D012015:Reference Standards
chemical_list: D055316:Cystatin C