Tamara van Donge

Reference intervals for kidney biomarkers in pediatrics 199 10 kidney function and injury marker values between age groups. Sex and weight associations were assessed using standard ANOVA. In case of multiple associations between the marker and demographic characteristics, a multivariate linear regression model was fitted. When a linear regression model did not capture the trend of the data, more complex models such as nonlinear and piecewise regression models were investigated. The Akaike Information Criterion (AIC) was used to guide model selection. Subsequently, the predicted means and 95% prediction intervals of all markers were computed based on the fitted regression model to determine the reference intervals. A correlation matrix was used to visualize the correlation among the different markers. R (version 3.5.1; R Development Core Team, Vienna, Austria, http://r-project.org) was used for data analysis and visual graphics. Results One hundred and fifty-eight children were enrolled of which 16 participants (10%) had to be excluded (withdrawn consent or no blood sampling prior to anesthesia, Table S1). In total, reference intervals for eight kidney function and injury markers from 142 pediatric subjects were determined. Study population The demographic and clinical characteristics of study participants are shown in Table 2. Median weight and height per age group were 9.8 kg and 76 cm (0–2 years), 16.5 kg and 103 cm (>2–5 years), 23 kg and 125 cm (>5–10 years) and 50 kg and 157 cm (>10–≤15 years). 37.3% were female, 92.3% were Caucasian and 9.2% were born preterm (mean gestational age of 35 weeks). The distribution for types of surgery changed for specific age groups (Table S2). In total, 20.4% of participants received medication or nutritional supplements in the 48 hours before surgery, of these 37.9% were treated with vitamin D and 55.2% of participants received their last dose one day prior the surgery (Table S3). Only 2% of participants were treated with drugs with potential nephrotoxic side effects (ibuprofen or isotretinoin, Table S3). Statistical analysis The mean (SD) values of for each marker of the total studied pediatric population were; ALB 38.2 (4.9) g/L, B2M 1.7 (0.4) mg/L, BTP 0.7 (0.2) mg/L, CYSC 0.9 (0.2) mg/L, KIM-1 2460.1 (3163.6) ng/L, NGAL 40.0 (19.7) µg/L, SCR 39.5 (16.0) µmol/L, and URO 152.7 (75.9) µg/L (Figure 1).