Tamara van Donge

Chapter 10 210 increase until adolescence. Previous studies showed a similar inverse age correlation with CYSC during the first year of life and a lower CYSC concentration in pre-pubertal children (4–12 year) as compared to adolescents (12–17 years). 35 In a previous study, significant differences have also been observed between sexes, with generally lower concentrations for girls. 35 Whether these discrepancies between sexes are of clinical relevance, remains to be investigated. The predicted reference intervals for serum neutrophil gelatinase- associated lipocalin (NGAL) and serum uromodulin (URO) were found to be independent of age in our study. In healthy individuals, serum NGAL is expressed at low concentrations, filtered by the glomerulus and reabsorbed by the proximal tubule. 34 Pediatric patients with acute kidney injury showed an increase in serum NGAL concentrations (median of 355 µg/L). 20 Our data showed significant correlations between some, but not all kidney markers (Figure S1). This suggests that partly different information on renal function may be obtained, although this needs further investigation and might be of particular interest in diseased populations. There are several limitations to this study. An association between CYSC concentrations and sex was observed over the entire study population, but it needs to be acknowledged that the female population was underrepresented in the youngest age group. We emphasize that a study with a larger sample size is required to draw more definitive conclusions on this potential sex effect. Furthermore, due to the rapid physiological changes between neonatal age and infanthood due to maturation, the sample size in the youngest age group with a relatively wide age range from 0 to 2 years might not be large enough to detect age-associated changes within this particular group. While our study examines kidney markers across a broad age range, others have focused their data on infants younger than 2 months of age and found similar results. 19,21 Additionally, we recognize that prediction interval point estimates of the different age groups overlap for all markers. Studies with larger sample sizes are required to confirm our results. It is important to distinguish between statistically significant and clinically relevant results. For instance, the effect of age on albumin concentrations, which was statistically significant, can be questioned in terms of clinical relevance. Several biomarkers in the pediatric population (e.g. hormone levels or whole blood values, such as hemoglobin) show age-dependency, whereas other laboratory parameters (e.g. C-reactive protein or erythrocyte sedimentation rate) do not show an age effect. Our findings are relevant for pediatric health care providers for the interpretation of kidney function and injury markers to help to distinguish between physiological effects or pathological states. In conclusion, this study provides age appropriate reference intervals for eight kidney function and injury markers in healthy pediatric population from 2 months until 15 years. In addition to the more commonly used markers such as ALB and SCR; B2M, BTP and KIM-1 show a decrease with age in the healthy pediatric population. CYSC was lower in