5.2.1. NGAL

Human NGAL, a ubiquitous 25 kDa protein, was initially isolated from human neutrophils [37]. NGAL is expressed in small amounts in cells other than neutrophils, including lung, spleen, and kidney cells, and is thought to inhibit bacterial growth, scavenge iron, and induce epithelial growth [38]. NGAL can be secreted by epithelial cells, and it is markedly elevated in patients exhibiting an inflammatory immune response and defects in lipid metabolism, intracellular iron transport, renal tubular repair, or differentiation of kidney progenitor cells into tubular epithelial cells [39]. In the kidney, NGAL is secreted into the urine from the ascending limb of the loop of Henle to the collecting ducts, being synthesized in the distal nephron [40]. NGAL is small, freely filtered, and easily assayed in urine. The urine NGAL level is an early and sensitive biomarker of kidney injury [41]. The serum or urine NGAL level is a clinically useful biomarker of various types of AKI, including AKI after kidney transplantation [42], contrast medium-induced AKI [43], and AKI in critical care settings [44]. In children with UUTO, urine NGAL levels are significantly higher in bladder urine and/or renal pelvic urine compared to controls, correlate inversely with worsening obstruction, and decrease after surgery (Table 1) [26,36,45–49]. The AUC-ROC value for UUTO in children is 0.61–0.90 for bladder urine NGAL [26,36,45–48]. In adults with UUTO, the urine NGAL level increases in those with obstructive nephropathy (AUC-ROCs of 0.70 for bladder urine and 0.76 for renal pelvic urine) and decreases after relief of the obstruction [23,50,51]. Serum NGAL levels are significantly higher than in controls [45,50]. However, the use of NGAL as a biomarker of kidney injury induced by UUTO has several limitations. Age affects the predictive performance: NGAL better predicts AKI in children than in adults [52]. Serum and urine NGAL levels may be influenced by conditions other than UUTO, including chronic hypertension, systemic infection, inflammation, anemia, hypoxia, or malignancy [53–55]. The many sources of NGAL can render it difficult to identify the underlying pathology [40].
