Particulate exposure and kidney health: Diversity Supplement Villarreal Hernandez

项目摘要/摘要 这项建议的总体目标是有助于理解原因、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，接触高浓度的空气污染物将与 农业工人有急性肾损伤，热应激和脱水会产生不良影响 肾脏生物标记物。我们进一步假设，这种损伤是通过加压素介导的损伤发生的。 路径。 与危地马拉一家大型农业综合企业合作，接触到大批甘蔗工人将使 一项研究描述了甘蔗工人接触颗粒物(PM)及其成分(二氧化硅， 草甘膦和金属)与包括脱水和热应激在内的个人因素有关。我们会 检查空气污染物暴露的个人贡献以及以下各项的综合贡献 暴露和个人危险因素，对肾功能障碍的影响。此外，我们还将调查以下机制的作用 加压素途径在慢性肾衰发病机制中的作用。这项研究将：a)调查一项未经探索的暴露 确定可能使农业工人面临肾脏发育风险的吸入暴露的途径 通过进行强有力的个人暴露评估来评估功能障碍，b)评估 暴露(S)和急性肾损伤，以及c)研究脱水和发热的潜在机制 压力会增加CKDu的风险，并伴随着肾脏毒物的暴露。 为了解决这一假设，提出了三个目标：目标1重点描述暴露于PM、二氧化硅、 危地马拉甘蔗工人体内的金属和草甘膦以及气象因素的影响 在个人曝光方面。我们将在员工中使用前瞻性、量化的个人测量方法。目标2将 职业性空气污染物暴露与肾脏影响生物标志物的关系 找出交叉轮班、肾功能恶化和炎症风险增加的工人。AIM 3将评估 环境和个体危险因素导致肾损伤的潜在机制。建议数 专家小组研究将在两个6个月的收获季节收集重复的可吸入颗粒物个人空气样本 60个工人小组，共计120名工人。首先，我们将收集基线问卷和临床数据， 受雇于危地马拉甘蔗种植园的参与者的生物样本。接下来，我们将 收集每个参与者在整个工作班次中的个人空气测量数据，以估计每天的空气流量 班次前后接触二氧化硅、草甘膦和重金属以及尿液和血液生物标记物 每名工人在两个季节有三个时间点。 这项研究的结果将导致大规模干预试验，这将有助于通过靶向预防CKDU 可在国际上传播的针对弱势人群的潜在治疗方法。

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 chronic kidney 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 research will: a) investigate an unexplored exposure pathway to identify inhalation exposures that may place agricultural workers at risk for the development of kidney dysfunction by conducting a robust personal exposure assessment, b) evaluate the relationship between exposure(s) and acute kidney injury, and c) examine underlying mechanisms by which dehydration and heat stress contribute to increased risk of CKDu in conjunction with nephrotoxicant exposures. To address this hypothesis, three aims are proposed: Aim 1 focuses on characterizing exposure to PM, silica, metals, and glyphosate in Guatemalan sugarcane workers and examining the impact of meteorological factors on personal exposure. We will use prospective, quantitative personal measurements in workers. Aim 2 will evaluate the relationship between occupational air contaminant exposure and kidney biomarkers of effect to identify workers with increased 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 workers, totaling 120 workers. First, we will collect baseline questionnaire and clinical data and biological samples from participants at the time of hire at a sugarcane plantation in Guatemala. Next, we will collect personal air measurements for each participant during the entire work shift to estimate daily airborne exposure to silica, glyphosate, and heavy metals, as well as urine and blood biomarkers pre- and post-shift at three time points for each worker during the two seasons. Results of this research will lead to large-scale intervention trials that will help to prevent CKDu by targeting potential therapeutic approaches for vulnerable populations that can be disseminated internationally.