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.