Air pollutants, heat exposure, and kidney health: A longitudinal study in women in Central America

空气污染物、热暴露和肾脏健康：针对中美洲女性的纵向研究

• 批准号: 10583301
• 负责人: LEE S NEWMAN
• 金额: $ 63.08万
• 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: 2023-04-01 至 2028-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10583301
• 关键词: Acute; Address; Affect; Agricultural Workers; Agriculture; Air Pollutants; Airborne Particulate Matter; Arsenic; Biological Markers; Biomass; Burn injury; C-reactive protein; Cadmium; Cellular Stress; Central America; Central American; Chronic; Chronic Kidney Failure; Collaborations; Communities; Cooking Practices; Country; Creatinine; Data; Dehydration; Development; Diabetes Mellitus; Diameter; El Salvador; Epidemic; Etiology; Exposure to; Female; Female Adolescents; Field Workers; Glomerular Filtration Rate; Goals; Guatemala; Harvest; Health; Heat Stress Disorders; Heat-Shock Proteins 70; Heavy Metals; Home; Hour; Household; Hydration status; Hypertension; Individual; Inflammation; Inhalation Exposure; Injury; Injury to Kidney; International; Intervention Trial; Kidney; Kidney Diseases; Knowledge; LCN2 gene; Latin American; Lead; Leukocytes; Link; Longitudinal Studies; Measures; Metals; Modification; Monitor; Morbidity - disease rate; Nicaragua; Nicaraguan; Nickel; Occupational; Outcome; Participant; Particulate Matter; Pathogenesis; Pathway interactions; Plants; Population; Prevalence; Prevention strategy; Recurrence; Renal function; Reporting; Research; Risk; Risk Factors; Saccharum; Seasons; Serum; Silicon Dioxide; Source; Stress; Sum; Techniques; Time; UMOD gene; Vulnerable Populations; Woman; Work; Working Women; agricultural community; air sampling; ambient air pollution; cohort; cooking; cytokine; experience; fine particles; kidney dysfunction; male; meter; mortality; neglect; nephrogenesis; nephrotoxicity; novel; pollutant; post gamma-globulins; prevent; prevent epidemics; rat KIM-1 protein; sample collection; systemic inflammatory response; therapy design; working men

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 epidemic of chronic kidney disease of unknown origin (CKDu). Our central hypothesis is that exposure to high concentrations of airborne contaminants will be associated with kidney injury, cellular stress, and systemic inflammation in females at-risk for CKDu in Guatemala and Nicaragua. Nearly all research to date has focused on males, neglecting preliminary data showing that females working in agriculture and living in agricultural communities in Central American countries are also affected by CKDu. Additionally, studies to date have largely overlooked consideration of air pollutants as contributors to CKDu etiology. Given community pathways the potentially high exposures among Central American women from i n-home cooking sources, ambient air pollution, and agricultural sources, this is an ideal population to explore these potential linking exposure with kidney injury. In this proposal, we will characterize occupational and non- occupational airborne exposures to particulate matter (PM), silica, and metals over repeat 8-hour monitoring periods in 200 female sugarcane workers across three years (Aim 1). We will conduct 8-hour monitoring for each participant at three time points, twice during the harvest, when exposure is highest, and once during the off- season. We will evaluate the relationships between individual exposures (PM, silica, and metals) and risk factors (heat stress and dehydration), mechanisms of injury (kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, and uromodulin), heat-associated and cellular stress (heat shock protein 70), and inflammation (C- reactive protein, white blood cells, and cytokines), and kidney biomarkers of effect (serum creatinine and cystatin C) both acutely (Aim 2) and longitudinally (Aim 3). In addition, we will utilize novel statistical techniques, Bayesian kernel machine regression (BKMR), weighted quantile sum (WQS) regression and/or quantile g-computation, to estimate the effects of airborne pollutant mixtures on kidney injury and inflammation (Sub Aim 2.1). The overall goal of the study is to increase understanding of risk factors for CKDu in females to facilitate future research and prevention strategies. The proposed research addresses a knowledge gap in understudied, highly exposed populations: female workers in Guatemala and Nicaragua. The individual, and combined, contributions of exposures and risk factors on biomarkers of kidney dysfunction, cellular stress, and inflammation will be examined in this study. This exposure conducting stress, stress a) investigate an unexplored pathway to identify inhalation exposures that may place female agricultural workers at risk by a robust personal exposure assessment; b) evaluate the relationship between exposure(s), cellular inflammation, and kidney injury; and c) examine underlying mechanisms by which dehydration and heat contribute to increased risk of kidney injury. Results will lead to research will: intervention trials that will help prevent CKDu by targeting approaches for vulnerable populations that can be disseminated in the US and 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 预防未知慢性肾病流行的潜在策略 起源 （CK杜）。 我们的 中心假设是，暴露于高浓度的空气污染物与肾病有关 危地马拉和尼加拉瓜有 CKDu 风险的女性的损伤、细胞应激和全身炎症。 迄今为止，几乎所有研究都集中在男性身上，忽视了初步数据显示，女性在工作中工作 中美洲国家的农业和农业社区的生活也受到 CKDu 的影响。 此外，迄今为止的研究在很大程度上忽视了空气污染物对 CKDu 的影响 病因学。给定 社区 途径 中美洲女性在家中烹饪的潜在风险较高， 环境空气污染和农业来源，这是探索这些潜力的理想人群 将暴露与肾损伤联系起来。在本提案中，我们将描述职业和非职业的特征 重复 8 小时监测中职业空气中颗粒物 (PM)、二氧化硅和金属的暴露情况 三年内 200 名女性甘蔗工人的经期（目标 1）。我们将对每个项目进行8小时监控 参与者在三个时间点，两次在收获期间，当暴露最高时，一次在休息期间 季节。我们将评估个体暴露（PM、二氧化硅和金属）与风险因素之间的关系 （热应激和脱水），损伤机制（肾损伤分子-1，中性粒细胞明胶酶相关 脂质运载蛋白和尿调节蛋白）、热相关应激和细胞应激（热休克蛋白 70）以及炎症（C- 反应蛋白、白细胞和细胞因子）和肾脏效应生物标志物（血清肌酐和胱抑素） C) 急性（目标 2）和纵向（目标 3）。此外，我们将利用新颖的统计技术，贝叶斯 核机回归 (BKMR)、加权分位数和 (WQS) 回归和/或分位数 g 计算，以 估计空气污染物混合物对肾损伤和炎症的影响（子目标 2.1）。整体 该研究的目标是增进对女性 CKDu 危险因素的了解，以促进未来的研究和 预防策略。拟议的研究解决了未充分研究、高度暴露的知识差距 人群：危地马拉和尼加拉瓜的女工。 暴露和危险因素对肾功能障碍生物标志物的单独和综合贡献， 本研究将检查细胞应激和炎症。这 接触 进行 压力， 压力 a) 调查一个未探索的 识别可能使女性农业工人面临风险的吸入暴露的途径 健全的个人暴露评估； b) 评估暴露、细胞之间的关系 炎症和肾损伤； c) 检查脱水和高温的潜在机制 导致肾损伤的风险增加。结果将导致 研究将： 干预试验将有助于预防 CKDu 的目标是针对弱势群体的方法，这些方法可以在美国和国际上传播。