5.2.4. NAG

NAG, a 130–140 kDa protein, is a lysosomal enzyme distributed in various human tissue [84]. NAG is not filtered through the glomeruli. In the kidney, it is found predominantly in lysosomes of proximal tubular cells. The small amount of NAG normally present in the urine is exocytosed by these cells. Although the function of NAG in the kidney remains unknown, it is a marker of tubular cell function or damage [85]. Increased NAG excretion in urine is caused exclusively by proximal tubular cell injury. Accumulating evidence indicates that urine NAG levels correlate with exposure to nephrotoxic drugs, delayed allograft nephropathy, diabetic nephropathy, and AKI [85]. Urine NAG levels are elevated in patients with upper urinary tract infection, nephrolithiasis, and reflux nephropathy [86,87]. In children with UUTO, urine NAG levels were significantly higher in those with hydronephrosis (with or without a vesicoureteral reflux) than healthy controls or cystitis patients [88,89]. The NAG level in renal pelvic urine is 7-fold higher and that in bladder urine 1.7-fold higher than in normal controls [89]. Mohammad found that the AUC-ROC value for bladder NAG was 0.67 in children with UUTO [68]. Skalova reported that although the urine NAG level was significantly higher in patients with hydronephrosis compared to healthy controls, there were no differences between children with unilateral and bilateral hydronephrosis and no correlation between the urine NAG level and the grade of hydronephrosis [90]. In summary, urine NAG levels usefully detect childhood UUTO but do not reflect its severity. In one study of adults with UUTO, levels of NAG in bladder and renal pelvic urine were 2.5- and five-fold higher than those of normal controls (AUC-ROC values of 0.74 for bladder urine and 0.91 for renal pelvic urine) and decreased after treatment [23].
