Tamara van Donge

General discussion and future perspectives 235 11 the early detection of drug-related kidney injury in neonates, infants and children. The need for additional pediatric studies focusing on kidney biomarkers, which is highlighted in Chapter 9 , is designed and conducted in Chapter 10 . Age-dependent references ranges for eight kidney function and injury markers in healthy infants, children and adolescents were characterized (n=148). This clinical pediatric trial showed that albumin and creatinine increased with age (p<0.01), whereas β 2 -microglobulin, β-trace protein and kidney injury marker-1 decreased with advancing age. Cystatin C showed dependency on sex (lower concentrations in females) and decreased with age until reaching approximately 1.8 years; thereafter a slight increase with age was seen. Neutrophil gelatinase associated lipocalin and uromodulin did not show any age dependency in this healthy pediatric population ( Chapter 10 ). The establishment of age-dependent reference intervals for kidney function and injury biomarkers in a healthy population will allow earlier detection of kidney injury in pediatric patients who are ill and/ or treated with nephrotoxic drugs. 29 0.5 1.0 1.5 2.0 0.003 0.01 0.03 0.1 0.3 1.0 3.0 10.0 Postnatal age (years) Creatinine concentration (mg/dL) Extreme preterm neonates (not exposed to ibuprofen) Extreme preterm neonates (exposed to ibuprofen) Preterm neonates (exposed to ibuprofen) Infants, children and adolescents (healthy) Figure 2: Creatinine concentrations (mg/dL) versus postnatal age (years, log-transformed) obtained from studies included in this thesis. Creatinine concentrations obtained from extreme preterm neonates with a birth weight less than 1 kg, either exposed to ibuprofen (yellow) or not (blue) ( Chapters 7 and 8 ). Preterm neonates, exposed to ibuprofen for the treatment of a patent ductus arteriosus (orange) ( Chapter 6 ). Healthy infants, children and adolescents (green) ( Chapter 10 ).