Particulate exposure and kidney health

颗粒物暴露与肾脏健康

• 批准号: 10116952
• 负责人: JOHN L. ADGATE
• 金额: $ 61.39万
• 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/10116952
• 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 Factors; Biological Markers; Blood; Blood Urea Nitrogen; Burn injury; Caliber; Canes; Chronic; Chronic Kidney Failure; Clinical; Collaborations; Communities; Creatinine; Cystatins; Data; Dehydration; Development; Disease; Disease Progression; Environmental Pollutants; Epidemic; Exposure to; Fibrinogen; Future; General Population; Goals; Guatemala; Guatemalan; Harvest; Health; Heat Stress Disorders; Heavy Metals; Herbicides; 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; Measurable; Measurement; Measures; Mediating; Metals; Meteorological Factors; Monitor; Morbidity - disease rate; Occupational; Occupational Exposure; Oils; Osmolalities; Outcome; Participant; Particulate; Particulate Matter; Pathogenesis; Pathway interactions; Pollution; Population; Prevalence; Prevention strategy; Questionnaires; Recurrence; Renal function; Research; Risk; Risk Factors; Role; Saccharum; Sampling; Seasons; Serum; Silicon Dioxide; Soil; Therapeutic; Thick; Time; Urine; Vasopressins; Vulnerable Populations; Weight; air contaminant; air sampling; amorphous silicate; base; cohort; cytokine; experience; exposure pathway; fine particles; glyphosate; improved; inflammatory marker; kidney dysfunction; longitudinal design; mortality; nephrotoxicity; pre-clinical; prevent; prospective; renal damage; shift work; sugar; therapy design; Acute; Acute Renal Failure with Renal Papillary Necrosis; Address; Administrative Supplement; Adverse effects; Affect; Agricultural Workers; Agriculture; Air; Air Pollutants; Air Pollution; Biological; Biological Factors; Biological Markers; Blood; Blood Urea Nitrogen; Burn injury; Caliber; Canes; Chronic; Chronic Kidney Failure; Clinical; Collaborations; Communities; Creatinine; Cystatins; Data; Dehydration; Development; Disease; Disease Progression; Environmental Pollutants; Epidemic; Exposure to; Fibrinogen; Future; General Population; Goals; Guatemala; Guatemalan; Harvest; Health; Heat Stress Disorders; Heavy Metals; Herbicides; 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; Measurable; Measurement; Measures; Mediating; Metals; Meteorological Factors; Monitor; Morbidity - disease rate; Occupational; Occupational Exposure; Oils; Osmolalities; Outcome; Participant; Particulate; Particulate Matter; Pathogenesis; Pathway interactions; Pollution; Population; Prevalence; Prevention strategy; Questionnaires; Recurrence; Renal function; Research; Risk; Risk Factors; Role; Saccharum; Sampling; Seasons; Serum; Silicon Dioxide; Soil; Therapeutic; Thick; Time; Urine; Vasopressins; Vulnerable Populations; Weight; air contaminant; air sampling; amorphous silicate; base; cohort; cytokine; experience; exposure pathway; fine particles; glyphosate; improved; inflammatory marker; kidney dysfunction; longitudinal design; mortality; nephrotoxicity; pre-clinical; prevent; prospective; renal damage; shift work; sugar; 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 预防未知来源的国际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 在农业工人中急性肾脏损伤，热应激和脱水会导致不利 对肾脏生物标志物的影响。我们进一步假设这种损害是通过加压素介导的 伤害途径。 与主要的危地马拉农业综合企业合作，进入甘蔗工人的群体将允许 对于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，我们将研究机械作用 CKDU发病机理的加压素途径。这 曝光途径 发展 关系 脱水 调查未探索的 确定有可能有风险的工人 通过进行强大的个人暴露评估来进行肾脏功能障碍，b）评估 在暴露和急性肾脏损伤之间，以及c）检查基本机制 热应激有助于增加CKDU的风险以及肾毒性暴露。 研究将： 一个） 吸入暴露于农业 到 金属， 在 评价 确认 解决了这一假设，提出了三个目标：目标1专注于表征暴露于PM的二氧化硅， 危地马拉甘蔗工人的草甘膦并检查气象因素的影响 个人暴露。我们将在工人中使用预期的，定量的个人测量。 AIM 2意志 职业空气污染物暴露与肾脏生物标志物之间的关系与 横移风险恶化的肾功能和炎症的风险中的工人。目标3意志 评估环境和个体危险因素诱导肾脏损伤的潜在机制。这 拟议的面板研究将在两个6个月的收获中收集重复可呼吸的PM个人空气样本 两组60的季节 临床 危地马拉。 数据和 下一个， 生物 工人，总计120名工人 参与者的样本 。第一的， 这 我们将收集基线问卷，并 在甘蔗种植园租用的时间 在整个工作中，我们将为每个参与者收集个人空气测量 估计每日空降暴露草甘膦，重金属以及尿液和血液 在两个赛季中，每个工人的换档前后生物标志物t三个时间点。 到 二氧化硅， 一个 这项研究的结果将领导Tolarge规模的干预试验，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。