Carobene Anna, Marino Irene, Coşkun Abdurrahman, Serteser Mustafa, Unsal Ibrahim, Guerra Elena, Bartlett William A, Sandberg Sverre, Aarsand Aasne Karine, Sylte Marit Sverresdotter, Røraas Thomas, Sølvik Una Ørvim, Fernandez-Calle Pilar, Díaz-Garzón Jorge, Tosato Francesca, Plebani Mario, Jonker Niels, Barla Gerhard, Ceriotti Ferruccio
Servizio di Medicina di Laboratorio, Ospedale San Raffaele, Milan, Italy;
Biological Variation Working Group, European Federation of Clinical Chemistry and Laboratory Medicine, http://efcclm.eu/science/wg-biological-variation, www.biologicalvariation.com.
Clin Chem. 2017 Sep;63(9):1527-1536. doi: 10.1373/clinchem.2017.275115. Epub 2017 Jul 18.
The European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) European Biological Variation Study (EuBIVAS) has been established to deliver rigorously determined biological variation (BV) indices. EuBIVAS determined BV for serum creatinine using the enzymatic and alkaline picrate measurement methods.
In total, 91 healthy individuals (38 males, 53 females; age range, 21-69 years) were bled for 10 consecutive weeks at 6 European laboratories. An equivalent protocol was followed at each center. Sera were stored at -80 °C before analysis. Analyses for each patient were performed in duplicate within a single run on an ADVIA 2400 system (San Raffaele Hospital, Milan). The data were subjected to outlier and homogeneity analysis before performing CV-ANOVA to determine BV and analytical variation (CV) estimates with confidence intervals (CI).
The within-subject BV estimates [CV (95% CI)] were similar for enzymatic [4.4% (4.2-4.7)] and alkaline picrate [4.7% (4.4-4.9)] methods and lower than the estimate presently available online (CV = 5.9%). No significant male/female BV differences were found. Significant differences were observed in mean creatinine values between men and women and between Turkish individuals and those of other nationalities. Between-subject BV (CV) estimates, stratified accordingly, produced CV values similar to historical BV data. CV was 1.1% for the enzymatic and 4.4% for alkaline picrate methods, indicating that alkaline picrate methods fail to fulfill analytical performance specifications for imprecision (CV).
The serum creatinine CV obtained by EuBIVAS specifies a more stringent CV than previously identified. The alkaline picrate method failed to meet this CV, raising questions regarding its future use.
欧洲临床化学与检验医学联合会（EFLM）的欧洲生物变异研究（EuBIVAS）旨在提供经过严格测定的生物变异（BV）指标。EuBIVAS使用酶法和碱性苦味酸盐测量法测定血清肌酐的BV。
总共91名健康个体（38名男性，53名女性；年龄范围21 - 69岁）在6家欧洲实验室连续10周采血。每个中心遵循相同的方案。血清在分析前储存在-80°C。对每位患者的分析在ADVIA 2400系统（米兰圣拉斐尔医院）上单次运行时重复进行两次。在进行CV方差分析以确定BV和带有置信区间（CI）的分析变异（CV）估计值之前，对数据进行异常值和同质性分析。
酶法[4.4%（4.2 - 4.7）]和碱性苦味酸盐法[4.7%（4.4 - 4.9）]的个体内BV估计值[CV（95%CI）]相似，且低于目前在线可得的估计值（CV = 5.9%）。未发现显著的男性/女性BV差异。男性与女性之间以及土耳其个体与其他国籍个体之间的肌酐均值存在显著差异。相应分层后的个体间BV（CV）估计值产生的CV值与历史BV数据相似。酶法的CV为1.1%，碱性苦味酸盐法的CV为4.4%，这表明碱性苦味酸盐法未能满足不精密度（CV）的分析性能规范。
EuBIVAS获得的血清肌酐CV比先前确定的更为严格。碱性苦味酸盐法未达到此CV，引发了对其未来使用的质疑。
