Mueller P W, Smith S J, Steinberg K K, Thun M J
Division of Environmental Health, Center for Environmental Health and Injury Control, Atlanta, Ga.
Nephron. 1989;52(1):45-54. doi: 10.1159/000185581.
In this study the urine activities of two brush border membrane enzymes, alanine aminopeptidase (AAP) and gamma-glutamyltranspeptidase (GGT), and the lysosomal enzyme N-acetyl-beta-D-glucosaminidase (NAG) were measured in men exposed to cadmium to investigate chronic renal toxicity. The subjects consist of a group with urine cadmium levels less than 2.0 micrograms/l and a group with higher cadmium levels (urine cadmium greater than or equal to 2.0 micrograms/l) with past or present occupational exposure to cadmium. The mean NAG value corrected for creatinine in the higher cadmium group (2.95 U/g creatinine) is significantly different from the mean low cadmium group value (0.92 U/g creatinine, p = 0.0083). Likewise, AAP in the higher group (13.83 U/g creatinine) is significantly different from that of the low group (6.58 U/g creatinine; p = 0.0018). NAG and AAP also give significant correlations with cadmium levels in urine (NAG: r = 0.51; p = 0.0001; AAP: r = 0.56; p = 0.0001). There is no similar statistically significant difference in GGT means in the two groups. In contrast to cadmium correlations, blood lead does not correlate with NAG, AAP, or GGT. A dose-response relationship was found between NAG and cadmium and between AAP and cadmium. The analysis of this relationship gives estimates of a 10% chance of observing an elevated NAG value at a cadmium level of 6.3 micrograms/g creatinine (8.0 micrograms/l) and a 10% chance of observing an elevated AAP at a cadmium level of 5.0 micrograms/g creatinine (3.4 micrograms/l). These data indicate elevations of NAG and AAP at urine cadmium levels below the level of 10 micrograms/g creatinine recommended as an upper limit by the 1980 World Health Organization Study Group. Since elevated levels of NAG and AAP in cadmium-exposed workers may reflect chronic renal tubular nephrotoxicity, these findings indicate that cadmium levels below 10 micrograms/g creatinine may be accompanied by subclinical tubular dysfunction, and that WHO guidelines should be interpreted cautiously, particularly with reference to workers who are no longer exposed and may have had higher cadmium body burdens in the past.
在本研究中，检测了接触镉的男性尿液中两种刷状缘膜酶（丙氨酸氨基肽酶[AAP]和γ-谷氨酰转肽酶[GGT]）以及溶酶体酶N-乙酰-β-D-氨基葡萄糖苷酶（NAG）的活性，以研究慢性肾毒性。研究对象包括两组，一组尿镉水平低于2.0微克/升，另一组镉水平较高（尿镉大于或等于2.0微克/升），这些人过去或现在有职业性镉接触史。镉水平较高组经肌酐校正后的NAG平均水平（2.95 U/g肌酐）与镉水平较低组的平均水平（0.92 U/g肌酐，p = 0.0083）有显著差异。同样，镉水平较高组的AAP（13.83 U/g肌酐）与镉水平较低组的AAP（6.58 U/g肌酐；p = 0.0018）有显著差异。NAG和AAP与尿镉水平也有显著相关性（NAG：r = 0.51；p = 0.0001；AAP：r = 0.56；p = 0.0001）。两组GGT的平均值没有类似的统计学显著差异。与镉的相关性不同，血铅与NAG、AAP或GGT均无相关性。在NAG与镉以及AAP与镉之间发现了剂量反应关系。对这种关系的分析表明，在肌酐镉水平为6.3微克/克（8.0微克/升）时，观察到NAG值升高的概率为10%；在肌酐镉水平为5.0微克/克（3.4微克/升）时，观察到AAP升高的概率为10%。这些数据表明，在尿镉水平低于1980年世界卫生组织研究小组推荐的10微克/克肌酐上限时，NAG和AAP就已升高。由于镉接触工人中NAG和AAP水平升高可能反映慢性肾小管肾毒性，这些发现表明，肌酐镉水平低于10微克/克时可能伴有亚临床肾小管功能障碍，并且世界卫生组织的指导方针应谨慎解读，尤其是对于不再接触镉且过去可能有较高镉体内负荷的工人。
