Tamara van Donge

Chapter 9 180 C values of 1650 ng/mL for preterm neonates of 29-36 weeks gestational age (Figure 2). 34 Armangil et al . demonstrated mean serum cystatin C differences in neonates between the first day of life (1800 ng/mL) and the third day of life (1650 ng/mL). 33 In the neonate, the tubular length is less than in the adult, thus the absolute proportion reabsorbed is likely to be less, which can influence the biomarker values. 34 Taken together, age dependent changes in serum cystatin C levels are observed from prematurity to childhood (Figure 2). Kidney injury molecule-1 (KIM-1) KIM-1 is a transmembrane glycoprotein which is expressed in low levels in healthy proximal tubule cells; hence it is thought to be a promising biomarker of proximal tubular injury. Researchers have shown that the time of measurement can influence urinary KIM-1 values, reflecting lower values in the evening in children. 19 In children aged 3 to 18 years, mean urinary KIM-1 values increase slightly from 336.8 to 515.6 pg/mL respectively, but did not show any differences due to the sex of the child. 18 Although median urinary KIM-1 values are significantly higher in preterm neonates (1910-3160 pg/mL), Saeidi et al . showed that urinary KIM-1 values did not correlate with gestational age in preterm neonates (Figure 2). 29 Besides age and sex, ethnicity can also play a role in the identification of renal reference values. 19 No data of serum KIM-1 is available fulfilling the inclusion criteria of this review. To conclude, age dependency in urinary KIM-1 values is observed, although a clear knowledge gap in young infants less than 3 years of age is recognized. Other KI biomarkers Beta-trace protein is a glycoprotein that is produced by glial cells in the central nervous system, and is freely filtered by the glomerulus and subsequently reabsorbed by the proximal tubule cells. 20 Serum beta-trace protein shows peak levels after birth and declines in the first year of life. 20 Serum beta-2 microglobulin is independent from muscle mass and the production of this protein is increased during infection and inflammatory processes. 31 Recent research showed that serum beta-2 microglobulin to assess glomerular filtration function might be less favorable in pediatric populations as compared to adults. 38 However, urinary beta-2 microglobulin might be more useful since beta-2 microglobulin is removed from the serum by glomerular filtration, but almost all of the filtered protein is reabsorbed in the proximal tubule. This results in a minimal urinary beta-2 microglobulin concentration. 39 Saeidi et al. analyzed a wide range of KI biomarkers in neonates and investigated the impact of GA and postnatal age on the values of these markers in urine. Postnatal age affects α-glutathione S-transferase, beta-2 microglobulin, cystatin C, clusterin, KIM-1, NGAL, osteoactivin, osteopontin, trefoil factor family protein 3 and vascular endothelial growth factor. In addition, gestational age affects cystatin C, endothelial growth factor, NGAL, osteopontin, trefoil factor family protein 3, uromodulin and vascular endothelial growth factor. 29