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.

项目摘要/摘要 该提案的总体目标是为理解原因，机制和 预防未知来源的慢性肾脏疾病国际流行病的潜在策略 （CKDU）。我们的中心假设是，暴露于高浓度的空气污染物将与 由于农业工人的急性肾脏损伤，热应激和脱水会产生不利影响 在肾脏生物标志物上。我们进一步假设这种损害是通过加压素介导的损伤发生的 路径。 与主要的危地马拉农业综合企业合作，进入甘蔗工人的人口将允许 一项表征甘蔗工人暴露于颗粒物（PM）及其成分的研究（二氧化硅， 草甘膦和金属）与个人因素（包括脱水和热应激）结合使用。我们将 检查空气污染物暴露的个人贡献，以及 暴露和个人危险因素，肾功能障碍。此外，我们将研究 CKDU发病机理的加压素途径。这项研究将：a）研究未开发的暴露 识别吸入暴露的途径，可能使农业工作者处于肾脏发展的危险中 通过进行强大的个人暴露评估，b）评估功能障碍 暴露和急性肾脏损伤，c）检查脱水和热量的潜在机制 压力会导致CKDU的风险增加，并结合肾毒性暴露。 为了解决这一假设，提出了三个目标：目标1专注于表征暴露于PM的二氧化硅， 金属和危地马拉甘蔗工人的草甘膦并检查了气象因素的影响 关于个人曝光。我们将在工人中使用预期的，定量的个人测量。 AIM 2意志 评估职业空气污染物暴露与肾脏生物标志物之间的关系 确定具有增加跨移风险恶化肾功能和炎症风险的工人。 AIM 3将评估 环境和个人危险因素诱导肾脏损伤的潜在机制。提议 面板研究将在两个6个月的收获季节中收集可重复的可呼吸PM个人空气样本 由60名工人组成的小组，总计120名工人。首先，我们将收集基线问卷和临床数据以及 在危地马拉的一个甘蔗种植园雇用时，参与者的生物样品。接下来，我们会的 在整个工作转移期间，为每个参与者收集个人空气测量 暴露于二氧化硅，草甘膦和重金属，以及尿液和血液生物标志物前和换档后 每个工人在两个赛季中的三个时间点。 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CKDU 可以在国际上传播的脆弱人群的潜在治疗方法。