title: Trueness verification of actual creatinine assays in the European market demonstrates a disappointing variability that needs substantial improvement. An international study in the framework of the EC4 creatinine standardization working group.
abstract: BACKGROUND
  The European In Vitro Diagnostics (IVD) directive requires traceability to reference methods and materials of analytes. It is a task of the profession to verify the trueness of results and IVD compatibility.
  
  
  METHODS
  The results of a trueness verification study by the European Communities Confederation of Clinical Chemistry (EC4) working group on creatinine standardization are described, in which 189 European laboratories analyzed serum creatinine in a commutable serum-based material, using analytical systems from seven companies. Values were targeted using isotope dilution gas chromatography/mass spectrometry. Results were tested on their compliance to a set of three criteria: trueness, i.e., no significant bias relative to the target value, between-laboratory variation and within-laboratory variation relative to the maximum allowable error.
  
  
  RESULTS
  For the lower and intermediate level, values differed significantly from the target value in the Jaffe and the dry chemistry methods. At the high level, dry chemistry yielded higher results. Between-laboratory coefficients of variation ranged from 4.37% to 8.74%. Total error budget was mainly consumed by the bias. Non-compensated Jaffe methods largely exceeded the total error budget. Best results were obtained for the enzymatic method. The dry chemistry method consumed a large part of its error budget due to calibration bias.
  
  
  CONCLUSIONS
  Despite the European IVD directive and the growing needs for creatinine standardization, an unacceptable inter-laboratory variation was observed, which was mainly due to calibration differences. The calibration variation has major clinical consequences, in particular in pediatrics, where reference ranges for serum and plasma creatinine are low, and in the estimation of glomerular filtration rate.
authors.affiliation: University Hospital, Gent, Belgium. joris.delanghe@ugent.be
authors.forename: Joris R
authors.initials: JR
authors.lastname: Delanghe
authors.forename: Christa
authors.initials: C
authors.lastname: Cobbaert
authors.forename: Marie-Madeleine
authors.initials: MM
authors.lastname: Galteau
authors.forename: Aimo
authors.initials: A
authors.lastname: Harmoinen
authors.forename: Rob
authors.initials: R
authors.lastname: Jansen
authors.forename: Rolf
authors.initials: R
authors.lastname: Kruse
authors.forename: Päivi
authors.initials: P
authors.lastname: Laitinen
authors.forename: Linda M
authors.initials: LM
authors.lastname: Thienpont
authors.forename: Birgitte
authors.initials: B
authors.lastname: Wuyts
authors.forename: Cas
authors.initials: C
authors.lastname: Weykamp
authors.forename: Mauro
authors.initials: M
authors.lastname: Panteghini
mesh_terms: D001774:Blood Chemical Analysis / Q000379:methods* / Q000592:standards; D003404:Creatinine / Q000097:blood*; D005060:Europe; D007391:International Cooperation; D012015:Reference Standards; D015203:Reproducibility of Results
chemical_list: D003404:Creatinine