Tamara van Donge

Chapter 10 198 Switzerland). URO (ELISA, Euroimmun, Luzern, Switzerland, kit specific standardization) and KIM-1 (ELISA, Cohesion Biosciences, London, UK, kit specific standardization) were assayed on a DSX instrument (Dynex technologies, Denkendorf, Germany). Finally, BTP (N Latex BTP, nephelometry, Siemens Diagnostics, Zurich, Switzerland, kit specific standardization) was measured on a BN2 instrument (Siemens Diagnostics, Zurich, Switzerland). Liquid control material was used for CREA (Biorad Laboratories, Crissier, Switzerland), BTP (Siemens Diagnostics, Zurich, Switzerland), NGAL (Bioporto diagnostics, Hellerup, Denmark), URO (Euroimmun, Luzern, Switzerland) and ALB (Biorad Laboratories, Crissier, Switzerland). For CYSC (Biorad Laboratories, Crissier, Switzerland), B2M (Biorad Laboratories, Crissier, Switzerland) and KIM-1 (Cohesion Boosciences, London, UK) lyophilized control material was used. Inter-assay coefficients of variation, as assessed with commercially available control materials, were the following, with at least two control level concentrations: <3.2% for ALB, <7.7% for B2M, <8.4% for BTP, <2.7% CREA enzymatic, <2.9% for CYSC, <9.1% for KIM-1, <3.5% for NGAL, <5.5% for URO. Statistical analysis Kidney function and injury marker values are presented as mean values with standard deviation (SD), median values with interquartile ranges (IQR) and minimum and maximum values. Categorical variables are presented as numbers with percentages. The eGFR is calculated according to the bedside Schwartz formula and additionally corrected for actual body surface area. 5,6 Measured SCR concentrations were compared to previously published age-specific SCR reference ranges retrieved from a healthy pediatric population. 24,25 The study population is descriptively analyzed for age, sex, weight, height, prematurity, drug exposure two weeks and 48 hours before surgery, and type of elective surgery. Sample size was defined to detect an 18% difference in URO concentrations between adjacent age groups (0-2 years, 2-5 years, 5-10 years and 10-≤15 years) with significance levels of 5% and 80% power (Supplemental Material). Prior to statistical analysis, outlying observations were removed in accordance with the recommendations of the Clinical and Laboratory Standards Institute (CLSI), as these extreme values potentially affect the estimation of reference intervals. 26 Outliers were identified by Tukey’s method where values within the distribution that are either less than Q1–1.5×IQR or greater than Q3+1.5×IQR, are defined as extreme values. 23,27 Values of markers which were not normally distributed were log transformed before analysis. The primary analysis for the study was an analysis of variance (ANOVA) comparing URO concentrations of the age groups. As secondary endpoints, the relationship between each marker and age was investigated using Pearson’s correlation coefficient. A linear regression model was fitted to determine associations between the individual markers and age. For the summary statistics, and in addition to ANOVA, the Kruskal-Wallis test was also used to determine if there were differences in (untransformed)