Associations of multiple metals with kidney outcomes in lead workers

Objectives Environmental exposure to multiple metals is common. A number of metals cause nephrotoxicity with acute and/or chronic exposure. However, few epidemiologic studies have examined the impact of metal coexposure on kidney function. Therefore, the authors evaluated associations of antimony and thallium with kidney outcomes and assessed the impact of cadmium exposure on those associations in lead workers. Methods Multiple linear regression was used to examine associations between ln-urine thallium, antimony and cadmium levels with serum creatinine- and cystatin-C-based glomerular filtration measures and ln-urine N-acetyl-beta-D-glucosaminidase (NAG). Results In 684 participants, median urine thallium and antimony were 0.39 and 0.36 mu g/g creatinine, respectively. After adjustment for lead dose, urine creatinine and kidney risk factors, higher ln-urine thallium was associated with higher serum creatinine- and cystatin-C-based estimates of glomerular filtration rate; associations remained significant after adjustment for antimony and cadmium (regression coefficient for serum creatinine-based estimates of glomerular filtration rate =5.2 ml/min/1.73 m(2); 95% CI=2.4 to 8.0). Antimony associations with kidney outcomes were attenuated by thallium and cadmium adjustment; thallium and antimony associations with NAG were attenuated by cadmium. Conclusions Urine thallium levels were significantly associated with both serum creatinine-and cystatin-C-based glomerular filtration measures in a direction opposite that expected with nephrotoxicity. Given similarities to associations recently observed with cadmium, these results suggest that interpretation of urine metal values, at exposure levels currently present in the environment, may be more complex than previously appreciated. These results also support multiple metal analysis approaches to decrease the potential for inaccurate risk conclusions.