Particulate exposure and kidney health

项目概要/摘要 本提案的总体目标是促进对原因、机制和 预防不明原因慢性肾脏病国际流行的可能策略 （CKDu）.我们的中心假设是，暴露于高浓度的空气污染物将与 急性肾损伤的农业工人和热应激和脱水会产生不利的 对肾脏生物标志物的影响。我们进一步假设这种损伤是通过加压素介导的 损伤途径 与危地马拉一家大型农业综合企业合作接触甘蔗工人， 对于表征甘蔗工人暴露于颗粒物质（PM）及其成分（二氧化硅， 草甘膦和金属）与个人因素，包括脱水和热应激有关。我们将 检查空气污染物暴露的单独贡献，以及 暴露和个人风险因素对肾功能障碍的影响。此外，我们还将研究 CKDu发病机制的加压素途径。这 暴露途径 发展 关系 脱水 探索一个未被探索的 确定可能面临风险的工人， 通过进行稳健的个人暴露评估来评估肾功能不全，B）评估 暴露与急性肾损伤之间的关系，以及c）检查 和热应激导致CKDu的风险增加与肾毒性暴露。 研究将： a）、 吸入暴露， 到 金属， 对 评价 识别 针对这一假设，提出了三个目标：目标1侧重于表征暴露于PM，二氧化硅， 和草甘膦在危地马拉甘蔗工人和检查气象因素的影响 个人暴露。我们将在工人中使用前瞻性、定量的个人测量。目标2将 职业性大气污染物暴露与肾脏生物标志物关系 交叉轮班的工人肾功能恶化和炎症的风险增加。目标3将 评估环境和个体危险因素诱导肾损伤的潜在机制。的 拟议的小组研究将在两个6个月的收获期间重复收集可吸入PM个人空气样本 两组60个赛季 临床 危地马拉. 数据和 接下来， 生物 工人，共计120名工人 参与者的样本， .第一、 的 我们将收集基线问卷， 在甘蔗种植园的租用时间， 我们将在整个轮班期间收集每个参与者的个人空气测量结果， 估计每日通过空气接触草甘膦、重金属以及尿液和血液 在两个季节中，每个工人在轮班前和轮班后的三个时间点进行生物标志物检测。 到 二氧化硅， 一 这项研究的结果将导致大规模的干预试验，这将有助于预防CKDu的目标， 可以在国际上传播的针对弱势群体的潜在治疗方法。

Project Summary/Abstract The overarching goals of this proposal are to contribute to the understanding of the causes, mechanisms, and potential strategies for prevention of the international epidemic of chronickidney disease of unknown origin (CKDu). Our central hypothesis is that exposure to high concentrations of air contaminants will be associated with acute kidney injury in agricultural workers and that heat stress and dehydration will produce adverse effects on kidney biomarkers. We further hypothesize that this damage occurs through a vasopressin-mediated injury pathway. Access to a population of sugarcane workers in cooperation with a major Guatemalan agribusiness will allow for a study that characterizes sugarcane worker exposure to particulate matter (PM) and it constituents (silica, glyphosate, and metals) in conjunction with personal factors, including dehydration and heat stress. We will examine the individual contribution of air contaminant exposure, as well as the combined contribution of exposure and personal risk factors, on kidney dysfunction. In addition, we will investigate the mechanistic role of the vasopressin pathway to pathogenesis of CKDu. This exposure pathway development relationship dehydration investigate an unexplored identify may workers at risk for the of kidney dysfunction by conducting a robust personal exposure assessment, b) evaluate the between exposure(s) and acute kidney injury, and c) examine underlying mechanisms by which and heat stress contribute to increased risk of CKDu in conjunction with nephrotoxicant exposures. research will: a) to inhalation exposures that place agricultural To metals, on evaluate identify address this hypothesis, three aims are proposed: Aim 1 focuses on characterizing exposure to PM, silica, and glyphosate in Guatemalan sugarcane workers and examining the impact of meteorological factors personal exposure. We will use prospective, quantitative personal measurements in workers. Aim 2 will the relationship between occupational air contaminant exposure and kidney biomarkers of effect to workers withincreased risk of cross-shift worsening renal function and inflammation. Aim 3 will evaluate the potential mechanism by which environmental and individual risk factors induce kidney injury. The proposed panel study will collect repeat respirable PM personal air samples across two 6-month harvest seasons in two groups of 60 clinical Guatemala. data and Next, biological workers, totaling 120 workers samples from participants at . First, the we will collect baseline questionnaire and time of hire at a sugarcane plantation in we will collect personal air measurements for each participant during the entire work shift to estimate daily airborne exposure glyphosate, and heavy metals, as well as urine and blood biomarkers pre- and post-shift t three time points for each worker during the two seasons. to silica, a Resultsof this research will lead tolarge-scale intervention trials that will help to prevent CKDu by targeting potential therapeutic approaches for vulnerable populations that can be disseminated internationally.