Tamara van Donge

Reference intervals for kidney biomarkers in pediatrics 197 10 Materials and Methods Study design This single center prospective observational study of consecutive healthy children was conducted at the University Children’s Hospital Basel, Switzerland between December 2018 and June 2019. Infants, children and adolescents aged between 0 and ≤15 years, including patients up to 15 years and 11 months were eligible for study participation if they were healthy, required a venous line for elective surgery/anesthesia during their stay at the short stay unit or ward, allowing one blood draw without additional venipuncture. Patients with chronic or congenital diseases were excluded, with exception of adolescents with mild to moderate acne vulgaris. Study protocol was approved by the local ethics committee (EKNZ BASEC 2016-00884). Parents were informed about the study verbally and in writing, and written informed consent was obtained. In addition to parental consent, children aged 8 to 14 years could sign voluntary. Adolescents aged ≥ 14 years were eligible to sign the informed consent themselves for studies of low risk (risk category A study). The study was performed in accordance with Good Clinical Practice and the principles of the Declaration of Helsinki. Participants were included based on stratification into four age groups; 0 to 2 years, >2 years to 5 years, >5 to 10 years and >10 to ≤15 years, in order to ensure a balanced age distribution. Demographic and clinical data and exposure to medication were collected on the day of study enrolment and at the day of surgery. Sample collection and lab assessment Blood samples were collected prior to (elective) surgery in lithium-heparin tubes. Samples were centrifuged (2500 g for 10 min at 20°C) within two hours after blood draw and serum was frozen at -20°C for a maximum of 24 hours, and subsequently stored at -80°C until analysis. Samples were stored for a maximum of eight months (stability was showed for a period of 12 months). Unique biomarkers were quantitated on the same day. Samples were processed at an ISO-17025 accredited medical laboratory, where eight serum kidney function and injury markers (ALB, BTP, B2M, SCR, CYSC, KIM-1, NGAL and URO) were measured. A minimum volume of 300 µL serum was required for analysis. ALB (Tina-quant® Albumin 2 nd generation, turbidimetric, standardized to BCR470/CRM470), SCR (IDMS-standardized), CYSC (Tina-quant® cystatin C 2 nd generation, turbidmetric, standardized to ERM-DA471/IFCC) and NGAL (particle-enhanced turbidimetric immunoassay, Bioporto diagnostics, Hellerup, Denmark, kit specific standardization), were measured with reagents from Roche Diagnostics (Rotkreuz, Switzerland) on a Cobas 6000 instrument (Roche Diagnostics, Rotkreuz, Switzerland). B2M (Tina-quant® β2-Microglobulin Roche, Rotkreuz, Switzerland) was determined on a Cobas 8000 instrument (Roche Diagnostics, Rotkreuz,