Chronic Renal Tubular Effects in Relation to Urine Cadmium Levels

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Abstract
In this study the urine activities of two brush border membrane enzymes, alanine aminopeptidase (AAP) and γ-glutamyltranspeptidase (GGT), and the lysosomal enzyme N-acetyl-β-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 < 2.0 μg/l and a group with higher cadmium levels (urine cadmium > 2.0 μg/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 μg/g creatinine (8.0 μg/l) and a 10% chance of observing an elevated AAP at a cadmium level of 5.0 μg/g creatinine (3.4 μg/l). These data indicate elevations of NAG and AAP at urine cadmium levels below the level of 10 μg/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 μg/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.