Neuman Gal, Nulman Irena, Adeli Khosrow, Koren Gideon, Colantonio David A, Helldén Anders
Division of Clinical Pharmacology & Toxicology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
J Clin Pharmacol. 2014 Jul;54(7):785-91. doi: 10.1002/jcph.281. Epub 2014 Mar 11.
Different serum creatinine (sCr) assays may obtain different values in the same patient, causing discrepancies in estimated glomerular filtration rate (eGFR) and sCr-based vancomycin dosing calculations.
To identify potential discrepancies in sCr concentrations obtained by different assays, the compensated Jaffe (sCr-Jaffe) and the enzymatic (sCr-enz), and to compare between the eGFR and vancomycin daily dose, based on these sCr values.
sCr-Jaffe and, sCr-enz concentrations of 890 healthy children, aged 1-18 years, were available from the Canadian Laboratory Initiative in Pediatric Reference Intervals study in Ontario. For each subject, eGFR (eGFR-Jaffe, eGFR-enz) was calculated using the revised Schwartz equation, and vancomycin daily dose (Vdose-Jaffe, Vdose-enz) was calculated using a sCr-based pharmacokinetic model.
Significant, age-related differences were found in sCr concentrations, and in subsequent eGFR and Vdose, between the two assays. In children aged 1-5 years, mean sCr-Jaffe was higher than sCr-enz (44.0 ± 5.0 vs. 27.7 ± 7.3 μmol/L, P < 0.001), leading to lower eGFR-Jaffe (83.2 ± 9.0 vs. 137.9 ± 27.1 mL/min/1.73m2, P < 0.001) and lower Vdose-Jaffe (44.7 ± 2.5 vs. 53.5 ± 5.1 mg/kg/24 h, P < 0.001).
Based on these findings, young children may be at risk for vancomycin under-treatment. Further research is needed to define the more accurate sCr assay in young children treated with renally excreted drugs.
不同的血清肌酐（sCr）检测方法可能在同一患者身上得出不同的值，从而导致估算肾小球滤过率（eGFR）以及基于sCr的万古霉素给药剂量计算出现差异。
识别不同检测方法（补偿性贾菲法[sCr-Jaffe]和酶法[sCr-enz]）所测得的sCr浓度之间的潜在差异，并基于这些sCr值比较eGFR和万古霉素每日剂量。
来自安大略省加拿大儿科参考区间实验室倡议研究的890名1至18岁健康儿童的sCr-Jaffe和sCr-enz浓度数据可用。对于每个受试者，使用修订后的施瓦茨方程计算eGFR（eGFR-Jaffe、eGFR-enz），并使用基于sCr的药代动力学模型计算万古霉素每日剂量（Vdose-Jaffe、Vdose-enz）。
两种检测方法在sCr浓度以及随后的eGFR和Vdose方面发现了与年龄相关的显著差异。在1至5岁儿童中，sCr-Jaffe的平均值高于sCr-enz（44.0±5.0对27.7±7.3μmol/L，P<0.001），导致eGFR-Jaffe较低（83.2±9.0对137.9±27.1mL/min/1.73m²，P<0.001）以及Vdose-Jaffe较低（44.7±2.5对53.5±5.1mg/kg/24h，P<0.001）。
基于这些发现，幼儿可能存在万古霉素治疗不足的风险。需要进一步研究以确定在接受经肾脏排泄药物治疗的幼儿中更准确的sCr检测方法。
