Urinary NAG in children with urolithiasis, nephrocalcinosis, or risk of urolithiasis

Abstract

A crucial role for cell-crystal interactions in the development of urolithiasis (UL) and nephrocalcinosis (NC) was previously observed in experiments with different cell lines mimicking renal epithelial cells. It was found that such cell-crystal interactions lead to tubular damage and/or or dysfunction. To find further proof for these observations, we measured the urinary N-acetyl-beta- d-glucosaminidase (NAG) excretion, a marker of proximal tubular damage, in children with UL or NC and in children with an increased risk of UL. We enrolled 142 children aged 4-16 years (mean 9.67+/-3.40 years), with 50 children having UL, 30 children with a history of UL (ULH), 20 patients with NC, 34 children with secondary hyperoxaluria (HyOx), and 8 children with idiopathic hypercalciuria (HC). Normal urinary NAG/Cr values were determined in a group of 70 healthy children aged 4-16 years (mean 10.06+/-3.97 years). The urinary NAG activity was measured using a colorimetric method and the results were expressed as molar creatinine (Cr) ratios. The highest median NAG/Cr ratios were found in children with UL plus hematuria (0.72 U/mM) and in children with UL (0.67 U/mM) or NC (0.48 U/mM), which were all significantly higher than those in controls (0.28 U/mmol, P<0.001 and P<0.05). The NAG/Cr ratios were increased above the upper normal reference interval of 0.63 U/mM (95th percentile) in 28 of 50 (56%) children with UL and in 9 of 20 (45%) children with NC. Although the ULH group also had significantly higher median NAG/Cr ratios (0.36 U/mM) compared with controls, the NAG/Cr ratio was only elevated in 4 of 30 (13%) patients. NAG values in children with secondary HyOx or HC were not different from controls. No correlation was found between the NAG/Cr ratios and the urinary excretion of oxalate or calcium. In conclusion, UL or NC may result in proximal tubular injury, which is rather the consequence of disease activity and of the mechanical influence of calculi, than of the metabolic background. The mechanism of cell damage in these conditions however, seems to be complex. Neither HyOx nor HC alone were sufficient to induce severe tubular damage expressed as an increase in NAG excretion in our patients.

Determination of Clara cell protein urinary elimination as a marker of tubular dysfunction

“…In children, however, there is still a great deal of debate on this subject. While some studies have reported an increased elimination of NAG in children with idiopathic hypercalciuria (IH) [37], in others, the percentage of children with IH with an increased urinary elimination of NAG [36] or a history of urolithiasis [38] is low. In our series, only 10.2% of the children with hypercalciuria or hypocitraturia had an increased urinary elimination of CC16.…”

Renal Tubular Dysfunction in Pediatric Urolithiasis: Proteomic Evidence

“…Children with hypercalciuria were found to have increased urinary concentration of N-acetyl-beta-D-glucosaminidase (NAG), a lysosomal enzyme considered to be a sensitive marker of proximal tubular injury (17). Calcium crystals may damage tubular epithelial cells affecting their function.…”

The Association between Urinary Tract Infection and Idiopathic Hypercalciuria in Children

“…8 In recent studies, remarkable improvement has been observed in the majority of these clinical conditions with the treatment of IHC. [8][9][10][11][12][13][14][15][16] Since many of these conditions including UTI may also lead to significant morbidity and mortality in children, identification of IHC is of great importance.…”