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

项目摘要/摘要 这项建议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脏病流行的可能策略 起源 (CKDu) 我们的 中心假设是，暴露在高浓度空气污染物中将与肾脏有关。 危地马拉和尼加拉瓜CKDu高危女性的损伤、细胞应激和全身炎症。 到目前为止，几乎所有的研究都集中在男性身上，忽略了初步数据显示，女性在 中美洲国家的农业和农业社区的生活也受到了CKDu的影响。 此外，到目前为止，研究在很大程度上忽略了空气污染物作为CKDU的贡献者的考虑 病因学。vt.给出 社区 路径 来自家庭烹饪来源的中美洲妇女中潜在的高风险暴露， 环境空气污染和农业污染源，这是探索这些潜力的理想人群 将暴露与肾脏损伤联系起来。在这份提案中，我们将区分职业和非职业 重复8小时监测的职业空气中颗粒物(PM)、二氧化硅和金属的暴露 对200名甘蔗女工人进行为期三年的月经(目标1)。我们将对每个人进行8小时的监测 参与者在三个时间点，两次在收获期间，在接触最多的时候，一次在休息时间- 赛季到了。我们将评估个人暴露(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(肾脏损伤分子-1，中性粒细胞明胶酶相关 脂钙蛋白和尿调蛋白)，热相关和细胞应激(热休克蛋白70)，以及炎症(C- 反应蛋白、白细胞和细胞因子)和肾脏生物标记物(血清肌酐和胱抑素 C)敏锐地(目标2)和纵向(目标3)。此外，我们将利用新的统计技术，贝叶斯 核机器回归(BKMR)、加权分位数和(WQS)回归和/或分位数g计算，以 评估空气污染物混合物对肾脏损伤和炎症的影响(子目标2.1)。整体而言 本研究的目的是增加对女性慢性肾功能不全危险因素的了解，以促进未来的研究和 预防策略。这项拟议的研究解决了未被研究、高度暴露的 人口：危地马拉和尼加拉瓜的女工。 暴露和风险因素对肾功能障碍生物标记物的单独和联合作用， 在这项研究中，将检查细胞应激和炎症。这 暴露 导电 压力， 压力 A)调查未勘探的 确定可能将女性农业工人置于危险境地的吸入暴露的途径 强有力的个人暴露评估；b)评估暴露之间的关系(S)， 炎症和肾脏损伤；以及c)检查脱水和发热的潜在机制 会增加肾脏损伤的风险。结果将导致 研究将： 干预试验将有助于预防 CKDu通过针对弱势群体的方法，可以在美国和国际上传播。

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.