Tamara van Donge

Chapter 9 178 Neutrophil gelatinase-associated lipocalin (NGAL) NGAL is a protein which is part of the innate immune system and is activated in neutrophils. 20 It limits bacterial growth by blocking the iron-containing siderophores. NGAL can promote tubular formation and might enhance tubule repair after acute kidney injury. In healthy subjects, circulating NGAL is filtered through the glomerulus, is subsequently captured by megalin (a low-density lipoprotein receptor-related protein 2), and reabsorbed by the proximal tubule. 17 NGAL can be measured both in urine and serum. When we investigate the reference values of urinary NGAL across the entire pediatric age range, there is a decreasing trend observable from preterm neonates to adolescents (Figure 2). In preterm neonates less than 30 weeks of gestational age, mean urinary NGAL values are between 210 and 298 ng/mL. In preterm neonates ≥30 weeks of gestational age, mean urinary NGAL values decrease to 48 ng/mL. 29 This gestational age dependency for urinary NGAL values in preterm neonates is likely due to abnormalities in tubular function, and the decline in urinary NGAL could be due to the fact that nephrogenesis is complete around 36 weeks of gestation, and additionally, continues postnatally. Therefore, premature neonates often are presented by higher baseline values due to immature tubular transport mechanisms. 2 Cangemi et al . investigated urinary NGAL values in newborns (<5 days postnatal age) and children (mean 80.7 months) and did not found any correlation between urinary NGAL and age. However, a significant difference between the urinary NGAL values of newborns (median 30.3 ng/mL) and children (median 4.6 ng/mL) was observed. 32 In contrast, Saeidi et al . revealed that in preterm neonates, postnatal age and gestational age affects the urinary NGAL concentration. 29 In four gestational age subgroups, mean urinary NGAL showed a decrease over the first four days of life. 29 When adjusted for age differences, significant sex differences are demonstrated in urinary NGAL concentration, being higher in female population. 18 Other research showed as well that urinary NGAL levels are significantly higher in female pediatric population compared to males, but this effect is only visible after the age of 10 years. 18,19 It has been hypothesized that this might be because of the contamination with vaginal secretion containing neutrophils, although this has not been confirmed. 36 Only one study investigated serum NGAL in children aged 0 to 5.9 years. In this population, median of 80 ng/mL serum NGAL was assessed and no effect of age effect was investigated. 37 In summary, when urinary NGAL values are combined for four different age groups; preterm neonates (<37 weeks gestational age and <1 month), term neonates (>37 weeks gestational age and <1 month), infants (>1 month and <3 years) and children (>3 and <20 years), a decrease in urinary NGAL values can be observed from prematurity to childhood, which illustrates the age-dependency of this KI biomarker (Figure 3).