Particulate exposure and kidney health

颗粒物暴露与肾脏健康

• 批准号: 10543484
• 负责人: JOHN L. ADGATE
• 金额: $ 58.61万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-01 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10543484
• 关键词: Acute; Acute Renal Failure with Renal Papillary Necrosis; Address; Administrative Supplement; Adverse effects; Affect; Agricultural Workers; Agriculture; Air; Air Pollutants; Air Pollution; Biological; Biological Markers; Blood; Blood Urea Nitrogen; Burn injury; Chronic; Chronic Kidney Failure; Clinical; Collaborations; Creatinine; Data; Dehydration; Development; Diameter; Disease; Disease Progression; Environmental Pollutants; Epidemic; Exposure to; Functional disorder; Future; General Population; Goals; Guatemala; Guatemalan; Harvest; Health; Heat Stress Disorders; Heavy Metals; Herbicides; High Prevalence; Hour; Humidity; Hydration status; Impairment; Individual; Inflammation; Inflammatory; Inhalation Exposure; Injury; Injury to Kidney; International; Intervention Trial; Investigation; Kidney; Kidney Diseases; LCN2 gene; Latin America; Lead; Life; Manuals; Measurable; Measurement; Measures; Mediating; Metals; Meteorological Factors; Monitor; Morbidity - disease rate; Occupational; Occupational Exposure; Osmolalities; Participant; Particulate; Particulate Matter; Pathogenesis; Pathway interactions; Pollution; Population; Prevention strategy; Questionnaires; Recommendation; Recurrence; Renal function; Research; Risk; Risk Factors; Role; Saccharum; Sampling; Seasons; Serum; Silicon Dioxide; Soil; Therapeutic; Thick; Time; Urine; Vasopressins; Vulnerable Populations; Weight; agricultural community; air contaminant; air sampling; amorphous silicate; cohort; cytokine; experience; exposure pathway; fine particles; glyphosate; improved; inflammatory marker; kidney dysfunction; longitudinal design; meter; mortality; nephrotoxicity; poor health outcome; post gamma-globulins; pre-clinical; prevent; prospective; renal damage; 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 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.

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战略 （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 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企业合作，接触甘蔗工人群体将允许 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 暴露途径 发展 关系 脱水 调查一个未探索的 识别可能面临风险的工人 通过进行强有力的个人暴露评估来评估肾功能障碍，b) 评估 暴露与急性肾损伤之间的关系，以及 c) 检查潜在机制 热应激与肾毒物暴露一起导致 CKDu 风险增加。 研究将： 一个） 吸入暴露会使农业 到 金属， 在 评价 确认 针对这一假设，提出了三个目标： 目标 1 侧重于描述 PM、二氧化硅、 危地马拉甘蔗工人中的草甘膦和检查气象因素的影响 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 职业空气污染物暴露与影响肾脏生物标志物之间的关系 工作人员跨班会增加肾功能恶化和炎症的风险。目标3将 评估环境和个体危险因素诱发肾损伤的潜在机制。这 拟议的小组研究将在两次为期 6 个月的收获中重复收集可吸入 PM 个人空气样本 季节分两组，每组 60 只 临床 危地马拉。 数据和 下一个， 生物 工人总数120人 参与者的样本 。第一的， 这 我们将收集基线调查问卷并 甘蔗种植园的雇用时间 我们将在整个工作班次期间收集每位参与者的个人空气测量值 估计每日空气中草甘膦、重金属以及尿液和血液的暴露量 两个季节中每个工人轮班前和轮班后三个时间点的生物标记。 到 二氧化硅, 一个 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。