Environmental exposure to metal mixtures and kidney disease

描述(申请人提供)：人类通过各种环境媒介接触到多种化学物质。环境政策是支离破碎的，主要是为了控制单一媒介中单一化学品的暴露。在最近几年的国家健康和营养检查调查之前，关于低水平人群接触多种化学品的信息一直有限。迫切需要关于化学混合物对健康影响的流行病学数据，以解释实际环境暴露对健康的影响。我们建议确定同时接触肾毒性金属混合物是否与肾脏疾病的临床措施有关。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。我们将在具有代表性的美国人口样本中检查金属混合物的暴露情况。这些金属是钡、镉、钴、铅、汞、钼和铀。这些金属是根据肾毒性和已知人群暴露的毒理学或流行病学证据来选择的。将描述受影响人口的人口统计和社会经济特征。我们将检验这一假设，即多重风险敞口在种族/民族或社会经济地位之间的分布是不同的。将制定一种混合暴露指标，以说明每种金属的肾毒性效力的差异。肾毒性的效力将从研究文献中确定。我们将检验另外两个假设：(1)毒性加权的混合物暴露指标将揭示种族/民族或社会经济地位的暴露差异；(2)混合暴露指标较高的人将降低肌酐清除率，估计肾小球滤过率，并增加尿白蛋白/肌酐比率。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，美国人群中混合暴露的特征是该项目的独特贡献。其次，肾脏疾病的负担不成比例地落在少数群体和贫困人口身上，这可能是由于接触不同的金属混合物造成的。第三，本研究论证了个人水平流行病学研究中提出的暴露评估设计。环境政策主要依赖于对单一化学品暴露的研究，而实际暴露于混合物。这项研究探讨了当前的环境政策是否保护公众健康。国家环境健康科学研究所在其2006-2011年战略计划中指出，最大的公共健康影响取决于开展与社会决策相关的研究。

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.