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儿童肾小球滤过率的评估

Estimation of glomerular filtration rate in children.

作者信息

Léger Frédéric, Bouissou François, Coulais Yvon, Tafani Mathieu, Chatelut Etienne

机构信息

Unité de Pharmacocinétique, Institut Claudius-Regaud, 20-24 rue du Pont-St-Pierre, 31052 Toulouse, France.

出版信息

Pediatr Nephrol. 2002 Nov;17(11):903-7. doi: 10.1007/s00467-002-0964-5. Epub 2002 Sep 11.

Abstract

The aim of this study was to develop a method to predict the glomerular filtration rate (GFR) in children by using the population pharmacokinetic approach. This powerful approach is widely used for drug development in order to study relationships between patients' characteristics (demographic, morphological, biological covariates) and pharmacokinetic parameters. For the first time, (51)Cr-EDTA plasma concentrations from 64 children (development data set) were analyzed using the Non-linear Mixed Effects Model (NONMEM) program to determine the most appropriate equation to relate (51)Cr-EDTA clearance (as a measurement of GFR) and patient characteristics. The most predictive equation was based on body weight, square height, and plasma creatinine (PCr, determined by the Jaffé method). This equation was then validated using the data from a further 33 patients. This equation produced estimates of GFR that were less biased and more precise than those obtained using the widely used Schwartz formula. The coefficient of correlation between estimated and actual GFR was 0.83, and the 10th to 90th percentiles for percentage errors were -20% to +30%. Finally, analysis of the whole data set (97 patients) led to an equation (i.e., GFR (ml/min)=[56.7 x Body weight (kg)+0.142 x Length(2)(cm)]/PCr ( microM)) very similar to that obtained from the development data set. This equation would be useful for estimating GFR in children when isotopic determination of the (51)Cr-EDTA clearance cannot be performed.

摘要

本研究的目的是开发一种利用群体药代动力学方法预测儿童肾小球滤过率(GFR)的方法。这种强大的方法广泛应用于药物研发,以研究患者特征(人口统计学、形态学、生物学协变量)与药代动力学参数之间的关系。首次使用非线性混合效应模型(NONMEM)程序分析了64名儿童(开发数据集)的(51)铬-乙二胺四乙酸(Cr-EDTA)血浆浓度,以确定将(51)Cr-EDTA清除率(作为GFR的一种测量指标)与患者特征相关联的最合适方程。最具预测性的方程基于体重、身高平方和血浆肌酐(PCr,采用Jaffé法测定)。然后使用另外33名患者的数据对该方程进行验证。与使用广泛应用的Schwartz公式获得的估计值相比,该方程得出的GFR估计值偏差更小且更精确。估计的GFR与实际GFR之间的相关系数为0.83,误差百分比的第10至90百分位数为-20%至+30%。最后,对整个数据集(97名患者)的分析得出了一个方程(即GFR(ml/min)=[56.7×体重(kg)+0.142×身高(2)(cm)]/PCr(微摩尔)),该方程与从开发数据集获得的方程非常相似。当无法进行(51)Cr-EDTA清除率的同位素测定时,该方程可用于估计儿童的GFR。

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