Longitudinal Study of Risk Factors for Mesoamerican Nephropathy among Agricultural Workers in El Salvador, Central America

项目摘要 在中美洲存在慢性肾病（CKD）的流行，并且患病率已经下降。 在过去的20年里不断增加。萨尔瓦多的肾脏疾病总死亡率最高， CKD是世界上最严重的疾病之一，CKD是工作年龄男性死亡的第二大原因。由于其独特 根据这些特征，这种疾病被称为中美洲肾病（Mesoamerican Nephropathy，MeN）。在美国和欧洲，CKD 常见于老年人群（年龄>60岁），对男性和女性的影响相同，主要是由于糖尿病和 高血压相比之下，在中美洲的某些地区，CKD不成比例地影响年轻男性， 似乎与糖尿病或高血压无关。农业工人受影响最大，但具体 原因仍然未知。这项研究的目的是调查暴露的潜在作用 除草剂草甘膦，重金属和热应激对甘蔗和玉米工人中MeN的风险 在萨尔瓦多。这项拟议的研究旨在确定草甘膦、热应激和/或肾毒性 金属，单独或组合，导致肾损伤。我们还将研究肾损伤的生物标志物 导致肾功能随时间下降。 研究结果可能有助于与这三个相关的职业和环境健康干预 暴露，以及有助于了解肾损伤的生物标志物，这可能是用于早期 检测和治疗，以减轻肾损伤和CKD风险。结果也可能告知其他CKD流行病 在我们的国家，包括印度和斯里兰卡，也有类似的特征。我们的目标 是：（1）在萨尔瓦多萨尔瓦多招募并建立一个300名甘蔗和玉米工人的队伍;（2）测量热量， 对工人进行身体检查，并收集尿液和血液样本，以确定接触的特征， 基线时的金属和草甘膦，肾损伤的生物标志物，以及暴露于热应激和肌肉损伤， （3）调查行业、工作任务、工作年限， 金属、草甘膦和热应激，作为30个月期间肾功能（eGFR）的预测因子;（4）银行 生物样本，以便将来分析出现的其他假设;以及（5）交流个体 队列参与者的肾功能结果，以及队列参与者的总体研究结果， 社区、公共卫生官员和公众。研究小组一直在计划这个纵向的 这项队列研究进行了近一年，与制糖米尔斯，制糖生产者协会，社区中心 (and在该国受影响最严重的沿海地区，玉米合作社高度集中， 他是2002年首次发表关于这种流行病的萨尔瓦多领先肾病学家， 职业健康医生，培训和支持萨尔瓦多的农业工人，领导实地小组， 以及萨尔瓦多大学的工作、健康和环境项目。

Project Summary There is an epidemic of chronic kidney disease (CKD) in Central America, and the prevalence has been increasing over the past 20 years. El Salvador has the highest overall mortality rate from kidney disease in the world, and CKD is the second leading cause of mortality among men of working age. Due to its unique characteristics, the disease is referred to as Mesoamerican Nephropathy (MeN). In the US and Europe, CKD is common in older populations (age>60), affects men and women equally, and is primarily due to diabetes and hypertension. In contrast, CKD in certain regions of Central America disproportionately affects younger men and appears to be unrelated to diabetes or hypertension. Agricultural workers are the most affected, but the specific cause(s) remains unknown. The goal of the proposed research is to investigate the potential roles of exposure to the herbicide glyphosate, heavy metals and heat stress on the risk of MeN among sugarcane and corn workers in El Salvador. The proposed study aims to determine whether glyphosate, heat stress and/or nephrotoxic metals, alone or in combination, cause kidney injury. We will also investigate whether biomarkers of kidney injury lead to decreased kidney function over time. Results of the study may contribute to occupational and environmental heath interventions related to these three exposures, as well as contribute to the understanding of kidney injury biomarkers, which may be used for early detection and treatment to mitigate kidney injury and CKD risk. Results may also inform other CKD epidemics with similar characteristics that have been described in our countries including India and Sri Lanka. Our aims are: (1) Recruit and establish a cohort of 300 sugarcane and corn workers in El Salvador; (2) Measure heat, conduct physical examinations of workers, and collect urine and blood samples to characterize exposure to metals and glyphosate at baseline, biomarkers of kidney injury, and exposure to heat stress and muscle damage, pre- and post-shift over three consecutive workdays; (3) Investigate industry, job task, duration of employment, metals, glyphosate and heat stress, as predictors of kidney function (eGFR) over a 30-month period; (4) Bank biological samples for future analysis of additional hypotheses as they emerge; and (5) Communicate individual kidney function results to cohort participants, and overall study results to cohort participants, the scientific community, public health officials and the general public. The research team has been planning this longitudinal cohort study for nearly a year, coordinating with sugar mills, the sugar producers association, a community center (and leader) in the most affected coastal region of the country where corn cooperatives are highly concentrated, the leading El Salvadoran nephrologist who first published on this epidemic in 2002, a well-respected occupational health physician who trains and supports agricultural workers in El Salvador to lead the field team, and the University of El Salvador program on work, health and the environment.