Particulate exposure and kidney health: Diversity Supplement Villarreal Hernandez

颗粒物暴露与肾脏健康：多样性补充剂 Villarreal Hernandez

• 批准号: 10770032
• 负责人: JOHN L. ADGATE
• 金额: $ 7.05万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-27 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10770032
• 关键词: Acute Renal Failure with Renal Papillary Necrosis; Address; Adverse effects; Agricultural Workers; Air; Biological; Biological Markers; Blood; Chronic Kidney Failure; Clinical Data; Dehydration; Development; Epidemic; Exposure to; Future; Goals; Guatemala; Guatemalan; Harvest; Health; Heat Stress Disorders; Heavy Metals; Individual; Inflammation; Inhalation Exposure; Injury; Injury to Kidney; International; Intervention Trial; Kidney; Latin America; Measurement; Mediating; Metals; Meteorological Factors; Morbidity - disease rate; Occupational; Occupational Exposure; Participant; Particulate; Particulate Matter; Pathogenesis; Pathway interactions; Population; Prevention strategy; Questionnaires; Renal function; Research; Risk; Risk Factors; Role; Saccharum; Sampling; Seasons; Silicon Dioxide; Therapeutic; Time; Urine; Vasopressins; Vulnerable Populations; air contaminant; air sampling; exposure pathway; glyphosate; kidney dysfunction; mortality; nephrogenesis; nephrotoxicity; pre-clinical; prevent; prospective; shift work; therapy design

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.

项目概要/摘要 该提案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病国际流行的潜在策略 （CK杜）。我们的中心假设是，暴露于高浓度的空气污染物将与 农业工人急性肾损伤以及热应激和脱水会产生不利影响 关于肾脏生物标志物。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 途径。 与危地马拉一家大型农业企业合作，接触甘蔗工人将有助于 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）以及个人因素，包括脱水和热应激。我们将 检查空气污染物暴露的个体贡献，以及空气污染物暴露的综合贡献 暴露和个人危险因素对肾功能障碍的影响。此外，我们将研究其机制作用 CKDu 发病机制的加压素途径。这项研究将：a) 调查未经探索的暴露 识别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）评估之间的关系 暴露和急性肾损伤，以及 c) 检查脱水和高温的潜在机制 压力与肾毒物暴露一起导致 CKDu 风险增加。 为了解决这一假设，提出了三个目标： 目标 1 侧重于描述 PM、二氧化硅、 危地马拉甘蔗工人体内的金属和草甘膦，并检查气象因素的影响 关于个人曝光。我们将对工人进行前瞻性、定量的个人测量。目标2将 评估职业空气污染物暴露与影响肾脏生物标志物之间的关系 识别交叉班次、肾功能恶化和炎症风险增加的工人。目标 3 将评估 环境和个人危险因素诱发肾损伤的潜在机制。拟议的 小组研究将在两个为期 6 个月的收获季节中重复收集可吸入 PM 个人空气样本 60名工人为一组，共计120名工人。首先，我们将收集基线问卷和临床数据， 参与者在危地马拉甘蔗种植园受雇时采集的生物样本。接下来，我们将 在整个工作班次期间收集每个参与者的个人空气测量值，以估计每天的空气传播情况 轮班前和轮班后接触二氧化硅、草甘膦和重金属以及尿液和血液生物标志物 两个季节中每个工人的三个时间点。 这项研究的结果将导致大规模的干预试验，通过靶向治疗来帮助预防 CKDu 可以在国际上传播的针对弱势群体的潜在治疗方法。