Séronie-Vivien Sophie, Bouissou François, Dattez Sophie, Coulais Yvon, Hanser Anne-Marie, Hym Bernadette, Chatelut Etienne
Department of Clinical Biology, Institut Claudius Regaud, Université Paul Sabatier, Toulouse, France.
Clin Chem Lab Med. 2008;46(2):215-8. doi: 10.1515/CCLM.2008.045.
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.
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.
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.
As long as there is no standardization of SCr measurements, population pharmacokinetics may be a powerful tool to model inter-assay variability.
当血清肌酐（SCr）检测结果与公式开发过程中所使用的检测方法相比存在偏差时，用于估算肾小球滤过率（GFR）的公式的准确性会降低。
对100名接受51Cr-乙二胺四乙酸清除率（CLEDTA）检测的儿童，分别采用碱性苦味酸法（经典苦味酸比色法检测肌酐）、改良碱性苦味酸法（COMP）、酶法（ENZ）和高效液相色谱法检测SCr。基于非线性混合效应模型（NONMEM）的群体药代动力学方法用于建立CLEDTA与生理病理/分析变量之间的关系模型。
与碱性苦味酸法检测值不同，使用施瓦茨公式计算GFR时，改良碱性苦味酸法和酶法检测的SCr存在较大偏差（中位数分别为+27.0%和+39.1%）。通过分析血浆[51Cr-乙二胺四乙酸]与时间的曲线得到的最佳方程为（n = 67）：CLEDTA（毫升/分钟）= 61.9×[SCr（微摩尔）/Theta]Psi×[年龄（岁）/13.4]0.522×（体重（千克）/44.2）0.233。与SCr检测方法相关的系数和指数分别为：碱性苦味酸法，Theta = 97.4，Psi = -0.757（-0.922；-0.592）；改良碱性苦味酸法，Theta = 85.3，Psi = -0.579（-0.681；-0.477）；酶法，Theta = 82.6，Psi = -0.560（-0.659；-0.460）。将该方程应用于33名儿童时，估算的CLEDTA（EDTA清除率）无显著偏差：改良碱性苦味酸法为+3.1%（-11.8；+11.4），酶法为+5.3%（-7.2；+16.4）。
只要SCr检测未实现标准化，群体药代动力学可能是一种强大的工具，用于模拟不同检测方法之间的变异性。
