Moriguchi J, Ezaki T, Tsukahara T, Furuki K, Fukui Y, Okamoto S, Ukai H, Sakurai H, Shimbo S, Ikeda M
Kyoto Industrial Health Association, 67 Nishinokyo-Kitatsuboicho, Nakagyo-ku, Kyoto, Japan.
Toxicol Lett. 2003 Aug 28;143(3):279-90. doi: 10.1016/s0378-4274(03)00181-4.
Comparative evaluation was made on alpha(1)-microglobulin (alpha(1)-MG), beta(2)-microglobulin (beta(2)-MG), retinol binding protein (RBP) and N-acetyl-beta-D-glucosaminidase (NAG), as a marker of renal tubular dysfunction after environmental exposure to cadmium (Cd), with special references to the effects of aging and correction for creatinine concentration. For this purpose, a previously established database of 817 never-smoking Japanese women (at the ages of 20 to 74 years) on hematological [hemoglobin, serum ferritin (FE), etc.] and urinary parameters [alpha(1)-MG, beta(2)-MG, creatinine (cr), and a specific gravity] was revisited. For the present analysis, the database was supplemented by the data on RBP and NAG in urine. The exposure of the women to Cd was such that the geometric mean Cd in urine was 1.3 microg/g cr. Among the four tubular dysfunction markers, NAG showed the closest correlation with Cd, followed by alpha(1)-MG and then beta(2)-MG, and RBP was least so although the correlations were all statistically significant. The observed values of the markers gave the best results, whereas correction for a urine specific gravity gave poorer correlation, and it was the worst when correction for creatinine concentration was applied. Age was the most influential confounding factor. The effect of age appeared to be attributable at least in part to the fact that both creatinine and, to a lesser extent, the specific gravity decreased as a function of age. Iron deficiency anemia of sub-clinical degree as observed among the women did not affect any of the four tubular dysfunction markers. In conclusion, NAG and alpha(1)-MG, rather beta(2)-MG or RBP, are more sensitive to detect Cd-induced tubular dysfunction in mass screening. The use of uncorrected observed values of the markers rather than traditional creatinine-corrected values is recommended when comparison covers people of a wide range of ages.
对α1微球蛋白（α1-MG）、β2微球蛋白（β2-MG）、视黄醇结合蛋白（RBP）和N-乙酰-β-D-氨基葡萄糖苷酶（NAG）进行了比较评估，这些指标作为环境暴露于镉（Cd）后肾小管功能障碍的标志物，并特别参考了衰老的影响以及对肌酐浓度的校正。为此，重新审视了一个先前建立的包含817名从不吸烟的日本女性（年龄在20至74岁之间）的血液学[血红蛋白、血清铁蛋白（FE）等]和尿液参数[α1-MG、β2-MG、肌酐（cr）和比重]的数据库。对于本次分析，该数据库补充了尿液中RBP和NAG的数据。这些女性的Cd暴露情况为尿中Cd的几何平均值为1.3μg/g cr。在这四种肾小管功能障碍标志物中，NAG与Cd的相关性最密切，其次是α1-MG，然后是β2-MG，RBP的相关性最小，尽管所有相关性均具有统计学意义。标志物的观测值给出了最佳结果，而对比重进行校正时相关性较差，应用肌酐浓度校正时最差。年龄是最具影响力的混杂因素。年龄的影响似乎至少部分归因于肌酐以及在较小程度上比重随年龄增长而降低这一事实。这些女性中观察到的亚临床程度缺铁性贫血并未影响这四种肾小管功能障碍标志物中的任何一种。总之，在大规模筛查中，NAG和α1-MG比β2-MG或RBP更能敏感地检测Cd诱导的肾小管功能障碍。当比较涵盖广泛年龄范围的人群时，建议使用标志物的未校正观测值而非传统的肌酐校正值。
