Environmental exposure to metal mixtures and kidney disease

描述（由申请人提供）：人类通过所有环境介质暴露于多种化学品。环境政策是零散的，主要是为了控制在单一介质中接触单一化学品。关于低水平人群接触多种化学品的信息一直很有限，直到最近几年的全国健康和营养检查调查。迫切需要关于化学混合物对健康影响的流行病学数据，以解释实际环境接触对健康的影响。我们建议确定同时暴露于肾毒性金属的混合物是否与肾脏疾病的临床措施相关。我们的长期目标是促进我们对混合物对健康影响的理解，并改善环境政策的科学基础。我们将在美国人口的代表性样本中检查金属混合物暴露。这些金属是钡、镉、钴、铅、汞、钼和铀。这些金属是根据肾毒性的毒理学或流行病学证据和已知的人群接触情况选择的。将描述暴露人群的人口统计学和社会经济特征。我们将检验多重暴露在人种/种族或社会经济地位中分布不同的假设。将开发一种混合物暴露度量，以说明每种金属肾毒性效力的差异。将根据研究文献确定肾毒性效价。我们将检查2个额外的假设：（1）毒性加权混合暴露指标将揭示人种/种族或社会经济地位的暴露差异;（2）具有较高混合暴露指标的患者肌酐清除率和估计肾小球滤过率降低，尿白蛋白-肌酐比值升高。我们将使用列联表分析、协方差分析和多元回归来检验我们的假设。这个项目的意义有三个方面。首先，美国人口接触混合物的特征是该项目的独特贡献。其次，肾脏疾病的负担福尔斯不成比例地落在少数民族和贫困人口身上，这可能是由于对金属混合物的不同暴露。第三，本研究论证了在个人水平流行病学研究中建议的暴露评估设计。环境政策主要依赖于对单一化学品接触的研究，而实际接触是混合物。这项研究旨在探讨当前的环境政策是否能保护公众健康。国家环境卫生科学研究所在其2006-2011年战略计划中指出，最大限度地发挥公共卫生影响取决于开展与社会决策有关的研究。

DESCRIPTION (provided by applicant): Human populations are exposed to multiple chemicals through all environmental media. Environmental policies are fragmented and were designed primarily to control exposures to single chemicals in a single medium. Information on low-level population exposure to multiple chemicals has been limited until recent years of the National Health and Nutrition Examination Survey. Epidemiological data on the health effects of chemical mixtures is urgently needed to interpret the health implications of actual environmental exposures. We propose to determine whether concurrent exposure to a mixture of nephrotoxic metals is associated with clinical measures of kidney disease. Our long-term goal is to advance our understanding of the health effects of mixtures and improve the scientific basis for environmental policy. We will examine metal mixture exposures in a representative sample of the US population. The metals are barium, cadmium, cobalt, lead, mercury, molybdenum, and uranium. These metals were selected on the basis of toxicological or epidemiological evidence of nephrotoxicity and known population exposure. Demographics and socio-economic characteristics of the exposed population will be described. We will test the hypothesis that multiple exposures are distributed differently across race/ethnicity or socio-economic status. A mixture exposure metric will be developed that accounts for differences in each metal's nephrotoxic potency. Nephrotoxic potency will be determined from research literature. We will examine 2 additional hypotheses: (1) the toxicity-weighted mixture exposure metric will reveal exposure disparities by race/ethnicity or socio- economic status; and (2) those with higher mixture exposure metrics will have reduced creatinine clearance and estimated glomerular filtration rates and increased urinary albumin-creatinine ratios. We will test our hypotheses using contingency table analysis, analysis of covariance, and multivariate regression. The significance of this project is three-fold. First, characterization of mixture exposure in the US population is a unique contribution of this project. Second, the burden of kidney disease falls disproportionately on minority and poor populations perhaps due to differential exposure to metal mixtures. Third, this research demonstrates the proposed exposure assessment design in individual-level epidemiological research. Environmental policies rest primarily on studies of single chemical exposure while actual exposures are to mixtures. This research addresses whether current environmental policies protect public health. The National Institute for Environmental Health Sciences stated in its 2006-2011 Strategic Plan that maximal public health impact depends on conducting research relevant to societal decision making.