title: Post-standardization of routine creatinine assays: are they suitable for clinical applications.
abstract: Introduction Reliable serum creatinine measurements are of vital importance for the correct classification of chronic kidney disease and early identification of kidney injury. The National Kidney Disease Education Programme working group and other groups have defined clinically acceptable analytical limits for creatinine methods. The aim of this study was to re-evaluate the performance of routine creatinine methods in the light of these defined limits so as to assess their suitability for clinical practice. Method In collaboration with the Dutch External Quality Assurance scheme, six frozen commutable samples, with a creatinine concentration ranging from 80 to 239  μmol/L and traceable to isotope dilution mass spectrometry, were circulated to 91 laboratories in four European countries for creatinine measurement and estimated glomerular filtration rate calculation. Two out of the six samples were spiked with glucose to give high and low final concentrations of glucose. Results Results from 89 laboratories were analysed for bias, imprecision (%CV) for each creatinine assay and total error for estimated glomerular filtration rate. The participating laboratories used analytical instruments from four manufacturers; Abbott, Beckman, Roche and Siemens. All enzymatic methods in this study complied with the National Kidney Disease Education Programme working group recommended limits of bias of 5% above a creatinine concentration of 100  μmol/L. They also did not show any evidence of interference from glucose. In addition, they also showed compliance with the clinically recommended %CV of ≤4% across the analytical range. In contrast, the Jaffe methods showed variable performance with regard to the interference of glucose and unsatisfactory bias and precision. Conclusion Jaffe-based creatinine methods still exhibit considerable analytical variability in terms of bias, imprecision and lack of specificity, and this variability brings into question their clinical utility. We believe that clinical laboratories and manufacturers should work together to phase out the use of relatively non-specific Jaffe methods and replace them with more specific methods that are enzyme based.
authors: 1 Department of Clinical Biochemistry, Harrogate District Foundation Trust, Harrogate, UK.
authors: Nuthar
authors: N
authors: Jassam
authors: 2 SKML and Department of Clinical Chemistry, Queen Beatrix Hospital, Winterswijk, the Netherlands.
authors: Cas
authors: C
authors: Weykamp
authors: 3 WEQAS, Cardiff and Vale University Health Board, Cardiff, UK.
authors: Annette
authors: A
authors: Thomas
authors: 4 Biomedical Research Center, Department of Laboratory Medicine, University Hospital of Padova, Padova, Italy.
authors: Sandra
authors: S
authors: Secchiero
authors: 4 Biomedical Research Center, Department of Laboratory Medicine, University Hospital of Padova, Padova, Italy.
authors: Laura
authors: L
authors: Sciacovelli
authors: 4 Biomedical Research Center, Department of Laboratory Medicine, University Hospital of Padova, Padova, Italy.
authors: Mario
authors: M
authors: Plebani
authors: 5 SKML and Department for Clinical Chemistry, Amphia Hospital, Breda, the Netherlands.
authors: Marc
authors: M
authors: Thelen
authors: 6 SKML and Department of Clinical Chemistry, Leiden University Medical Center, Leiden, the Netherlands.
authors: Christa
authors: C
authors: Cobbaert
authors: 7 Quality Coordinator of Clinical Laboratory, Hospital Vall d'Hebron, Barcelona, Spain.
authors: Carmen
authors: C
authors: Perich
authors: 8 Spanish Society of Clinical Chemistry and Molecular Pathology (SEQC), Analytical Quality Commission, Barcelona, Spain.
authors: Carmen
authors: C
authors: Ricós
authors: 9 Department of Epidemiology, Unity of External Quality Assessment, National Health Institute Doutor Ricardo Jorge, Lisbon, Portugal.
authors: Faria A
authors: FA
authors: Paula
authors: 10 Department of Clinical Biochemistry, Leeds Teaching Hospitals Trust, Leeds, UK.
authors: Julian H
authors: JH
authors: Barth
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000175:diagnosis*; D016477:Artifacts; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D003124:Colorimetry / Q000706:statistics & numerical data; D003404:Creatinine / Q000097:blood*; D057075:Enzyme Assays / Q000295:instrumentation / Q000592:standards* / Q000706:statistics & numerical data; D005062:European Union; D005919:Glomerular Filtration Rate; D006801:Humans; D015588:Observer Variation; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000175:diagnosis*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D003404:Creatinine
keywords: Enzymatic methods; analytes; creatinine; laboratory methods