Sikora Przemyslaw, Glatz Sara, Beck Bodo B, Stapenhorst Ludwig, Zajaczkowska Malgorzata, Hesse Albrecht, Hoppe Bernd
Division of Pediatric Nephrology, University Children's Hospital, Josef-Stelzmann Strasse 9, 50924 Cologne, Germany.
Pediatr Nephrol. 2003 Oct;18(10):996-9. doi: 10.1007/s00467-003-1229-7. Epub 2003 Aug 13.
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.
先前在使用模拟肾上皮细胞的不同细胞系进行的实验中观察到细胞 - 晶体相互作用在尿路结石（UL）和肾钙质沉着症（NC）发展中起关键作用。研究发现，这种细胞 - 晶体相互作用会导致肾小管损伤和/或功能障碍。为了进一步证实这些观察结果，我们测量了UL或NC患儿以及UL风险增加患儿的尿N - 乙酰 - β - D - 氨基葡萄糖苷酶（NAG）排泄量，这是近端肾小管损伤的一个标志物。我们纳入了142名4至16岁的儿童（平均9.67±3.40岁），其中50名儿童患有UL，30名有UL病史（ULH），20名患者患有NC，34名儿童患有继发性高草酸尿症（HyOx），8名儿童患有特发性高钙尿症（HC）。在一组70名4至16岁（平均10.06±3.97岁）的健康儿童中测定了正常的尿NAG/Cr值。使用比色法测量尿NAG活性，结果以摩尔肌酐（Cr）比值表示。在患有UL加血尿的儿童（0.72 U/mM）、患有UL的儿童（0.67 U/mM）或患有NC的儿童（0.48 U/mM）中发现最高的中位数NAG/Cr比值，这些均显著高于对照组（0.28 U/mmol，P<0.001和P<0.05）。50名UL患儿中有28名（56%）和20名NC患儿中有9名（45%）的NAG/Cr比值高于正常参考区间上限0.63 U/mM（第95百分位数）。虽然与对照组相比，ULH组的中位数NAG/Cr比值也显著更高（0.36 U/mM），但30名患者中只有4名（13%）的NAG/Cr比值升高。继发性HyOx或HC患儿的NAG值与对照组无差异。未发现NAG/Cr比值与草酸或钙的尿排泄之间存在相关性。总之，UL或NC可能导致近端肾小管损伤，这更可能是疾病活动和结石机械影响的结果，而非代谢背景的结果。然而，在这些情况下细胞损伤的机制似乎很复杂。在我们的患者中，单独的HyOx或HC都不足以诱导以NAG排泄增加表示的严重肾小管损伤。
