Enzymatic but not compensated Jaffe methods reach the desirable specifications of NKDEP at normal levels of creatinine. Results of the French multicentric evaluation.

The French Society of Clinical Biochemistry conducted this study to compare the accuracy and performances of the best creatinine enzymatic assays and the compensated Jaffe methods from the same manufacturers. Creatinine was measured in 3 serum pools with creatinine levels of 35.9±0.9 µmol/L, 74.4±1.4 µmol/L, and 97.9±1.7 µmol/L (IDMS determination). The performances of the assays (total error that includes the contribution of bias and imprecision) were evaluated using Monte-Carlo simulations and compared against desirable NKDEP criteria. The enzymatic assays always fell within the desirable total Error of 7.6%. By contrast, this requirement was never obtained for the compensated Jaffe methods at the critical level of 74.4±1.4 µmol/L. Only the compensated Jaffe creatinine on Olympus analyzer reached this specification at 35.9±0.9 and 97.9±1.7 µmol/L levels. This study demonstrates that, despite substantial improvement regarding traceability to the IDMS reference method and precision, compensated Jaffe creatinine methods, by contrast to enzymatic ones, do not reach the desirable specifications of NKDEP at normal levels of creatinine.

A multicentric evaluation of IDMS-traceable creatinine enzymatic assays.

Chronic kidney disease definition is based on glomerular filtration rate (GFR) estimations which are derived from creatinine-based equations. The accuracy of GFR estimation is thus largely dependent of those of serum creatinine assays. International recommendations highlight the need for traceable creatinine assays. The French Society of Clinical Biochemistry conducted a study for measuring accuracy of creatinine enzymatic methods. This evaluation involved 25 clinical laboratories. Creatinine was measured in serum pools ranging from 35.9±0.9 µmol/L to 174.5±3.1 µmol/L (IDMS determination) using 12 creatinine enzymatic methods. For all creatinine values greater than 74.4±1.4 µmol/L, the bias and imprecision did not exceed 5% and 5.9%, respectively. For the lowest value (35.9±0.9 µmol/L), the bias ranged from -1.8 to 9.9% (with one exception). At this level, the imprecision ranged from 1.9 to 7.8%. The true performances of the assays (couples of bias and relative standard deviation), were evaluated using Monte-Carlo simulations. Most of the assays fall within the maximum Total Error of 12% at all concentrations. This study demonstrates substantial improvements in the calibration, traceability and precision of the enzymatic methods, reaching the NKDEP recommendations. Moreover, most of these assays allowed accurate creatinine measurements for creatinine levels lower than 40 µmol/L.

[Recommendations for the selection and alignment techniques for the determination of creatinine]. / Recommandations pour le choix et l'harmonisation des techniques de dosage de la créatinine.

In 2010, a working group from the French Society of Clinical Chemistry (Société française de biologie clinique - SFBC) and the French Society of Nephrologie (SN) make a proposal to up-date the guidelines for measuring plasma creatinine.

Modeling the variability of creatinine measurements improves estimates of the glomerular filtration rate.

BACKGROUND: The precision of the formulae used to estimate glomerular filtration rate (GFR) decreases when the serum creatinine (SCr) assay is biased compared with the assay used during the development of the formulae. METHODS: For 100 children referred for 51Cr-EDTA clearance (CLEDTA), SCr was measured with a JAFFE (classic Jaffe colorimetric creatinine assay), a compensated Jaffe (COMP), an enzymatic (ENZ) and an HPLC assay. A population pharmacokinetics approach based on a non-linear mixed effects model (NONMEM) was used to model the relationships between the CLEDTA and physiopathological/analytical variables. RESULTS: Unlike JAFFE values, COMP and ENZ SCr gave a high bias using the Schwartz formula for the GFR calculation (median +27.0% and +39.1%, respectively). The best equation obtained from the analysis of the curves of [51Cr-EDTA]plasma vs. time was (n=67): CLEDTA (mL/min)=61.9 x [SCr (microM)/Theta]Psi x [age (years)/13.4]0.522 x (weight (kg)/44.2)0.233. The SCr assay-related coefficients and exponents were Theta=97.4, Psi=-0.757 (-0.922; -0.592) for JAFFE; Theta=85.3, Psi=-0.579 (-0.681; -0.477) for COMP; and Theta=82.6, Psi=-0.560 (-0.659; -0.460) for ENZ. When applied to 33 children, this equation estimated CL(EDTA) without any significant bias: +3.1% (-11.8; +11.4) for COMP and +5.3% (-7.2; +16.4) for ENZ. CONCLUSIONS: As long as there is no standardization of SCr measurements, population pharmacokinetics may be a powerful tool to model inter-assay variability.

Impact of standardized calibration on the inter-assay variation of 14 automated assays for the measurement of creatinine in human serum.

PURPOSE: The aim of our study was to measure the inter-assay variation and accuracy of serum creatinine assays and to assess the effect of standardized calibration procedures on this variability. METHODS: We analyzed 30 human sera and three reference materials, using 17 creatinine assays (12 colorimetric, 4 enzymatic and 1 HPLC). We compared two standardized calibration procedures, using either a reference material or secondary standards, to that recommended by the manufacturers. RESULTS: For assays calibrated according to the manufacturers' recommendations, the median inter-assay coefficient of variation (CV) was 14.2% for 20 low samples (45-150 microM), and 7.7% for 10 high samples (250-350 microM). The CV was significantly influenced by the calibration procedure, but none of the standardized calibration procedures significantly improved the inter-assay variability. However, a significant decrease in CV was noted within each type of assay method (colorimetric or enzymatic) when the standardized calibration used standards of level(s) close to the concentrations to be measured. Only the compensated Jaffe technique and the amido-hydrolase assay showed bias of less than 10%. CONCLUSIONS: Standardizing calibration procedures is unlikely to decrease the analytical variability of creatinine assays enough to allow uniform and reliable use of the equations for estimation of glomerular filtration rate.