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 vari-

A multicentric evaluation of IDMS-traceable creatinine enzymatic assays

“…In this study, the budget of the total error was especially consumed by the systematic bias. This fact is especially relevant in enzymatic methods because the random measurement error is low with these methods [6]. Indeed, analytical performances of the enzymatic creatinine measurement are clearly better than for the classical Jaffe methods [10,11].…”

“…This observation confirms and extends Delanghe's previous report showing a constant overestimation using dry chemistry. Interestingly, after Delanghe's work, performed in 2005 [6], OrthoClinical Diagnostics has recalibrated its assay leading to an IDMS traceable creatinine. This process prevents the overestimation in value greater than 77 μmol/L (0.87 mg/dL), but has to be further improved for low values.…”

“…Our comparison has been realized against a valid and strong reference method and we used frozen human sera to avoid matrix effect [23,24]. Contrary to other studies, each method has been studied and validated in the same number of laboratories and with the same methodology which makes easier statistical interpretations [5,6]. However, there are some limitations.…”

“…They showed that a significant bias versus isotope dilution mass spectrometry (IDMS) value persisted [5]. More recently, the EC4 (European Communities of Clinical Chemistry) creatinine standardization working group showed that inter-laboratory variation persisted in reference material prepared from human fresh serum with sCr at a concentration of 76 μmol/L [6].…”

Estimation of renal function in patients with chronic kidney disease

“…However, the overestimation of GFR which might arise from the additional tubular secretion is to some degree counterbalanced by the overestimation of plasma creatinine (up to 20%) by interference of noncreatinine chromogens by the Jaffe's kinetic rate colorimetric reaction, which is the most commonly used method for the assessment of creatinine. Indeed, creatinine measurements by the unmodified Jaffe method are in general significantly higher as compared to the reference method, gas chromatography-isotope dilution mass spectrometry (GC-IDMS), whereas results obtained by the modified Jaffe reaction are generally in better agreement with the reference method (15). Also, the generation rate of creatinine in the body may not always be constant, and may be influenced by factors such as dietary intake (1).…”