The NINOS cohort: Children's Kidney Health in a High-Risk Region for CKDu

项目摘要/摘要 中美洲肾病(男性)是中美洲的主要死亡原因，导致超过 在过去的20年里，有2万人死亡。尽管对风险因素进行了十年的研究，包括高温和 随后的脱水、传染病、接触化学物质、服药和饮食，导致这种情况的原因 毁灭性的疾病仍不清楚。大多数受影响的人是从事农业工作的年轻人。 工业，特别是甘蔗。与世界其他地区的慢性肾脏疾病(CKD)不同，男性 以起病早为特点，患者确诊年龄在20多岁或更年轻。我们波士顿大学的研究 自2009年以来一直在中美洲领导男性研究的团队，已经确定了肾脏损伤和 该地区年轻人的肾功能下降，包括低EGFR的患病率升高和 高滤过和尿液中肾脏损伤的生物标志物，两者都可能提示早期肾脏疾病。我们的 初步数据使我们假设，早期生命、肾毒性暴露会导致肾脏损伤和 肾功能下降，这些暴露增加了男性在职业后的易感性 在以后的生活中暴露。2016年(基线)，我们团队在尼加拉瓜招募和招募了800多名青年，年龄 7-18岁，为儿童、青少年和青年纵向队列奠定基础( “NI-OS”队列)。在今年的R01中，我们建议对这些12-28岁的青少年进行跟踪调查 在研究开始时，为期36个月。这项研究的目标是：1)表征肾功能 青年和成年期间(EGFR的年化变化)尼加拉瓜，这是一个男性高危地区；2) 使用高通量蛋白质组学分析，包括&gt；180蛋白质，开发一个预测升高的生物标记物。 随着时间的推移，EGFR的年化下降；3)建立广泛的化学物质之间的联系 以及使用标准分析技术和“混合”分析技术的EGFR年化变化的重金属；4) 使用硅胶腕带进行多种化学暴露分析，包括&gt；1500化学物质，以广泛 评估个人接触化学品与肾功能之间的关系；以及4)评估 应用个人热暴露监测研究青年热暴露与肾功能之间的关系。 该项目将提供迄今为止关于肾功能和环境的最全面的说明。 疾病发作前男性高危人群中的暴露，提供了至关重要的病因 推论。原因不明的慢性肾脏疾病是一种全球公共卫生危机，同时也是一种流行病。 在斯里兰卡、埃及和印度，以及整个中美洲。这项研究将向国际社会提供 努力了解这一现象并减少发病率。

PROJECT SUMMARY/ABSTRACT MesoAmerican Nephropathy (MeN) is a leading cause of death in Central America, resulting in more than 20,000 deaths in the last 20 years. Despite a decade of research on risk factors, including heat and subsequent dehydration, infectious diseases, chemical exposures, medications and diet, the causes of this devastating disease remain unclear. The majority of affected individuals are young men working in agricultural industries, notably sugarcane. Unlike chronic kidney disease (CKD) in other parts of the world, MeN is characterized by early onset, with patients diagnosed in the 20s or younger. Our Boston University research team, which has led MeN research in Central America since 2009, has identified evidence of kidney injury and renal function decline among youth in the region, including elevated prevalence of low eGFR and evidence of hyperfiltration and urinary biomarkers of kidney injury, both of which may indicate early kidney disease. Our preliminary data leads us to hypothesize that early life, nephrotoxic exposures contribute to kidney injury and renal function decline, and that these exposures increase susceptibility to MeN following occupational exposures later in life. In 2016 (baseline), our team recruited and enrolled over 800 youth in Nicaragua, ages 7-18 years, to set the foundation for a longitudinal cohort of children, adolescents and young adults (the “NIÑOS” cohort). In this R01, we propose to initiate follow up with these youth, who will be 12-28 years of age at the start of the study, for a 36-month period. The goals of this study are to: 1) characterize renal function during youth and young adulthood (annualized change in eGFR) in Nicaragua, a region of high-risk for MeN; 2) use high-throughput proteomic analysis, including >180 proteins, to develop a predictive biomarker of elevated annualized decline in eGFR over time; 3) establish the association between a broad spectrum of chemicals and heavy metals with annualized change in eGFR, using standard and “mixtures” analytic techniques; 4) conduct a multichemical exposome analysis, including >1500 chemicals, using silicone wristbands to broadly evaluate the association between personal chemical exposure and renal function; and 4) assess the association between exposure to heat and renal function in youth using personal heat exposure monitoring. This project would provide the most comprehensive account to date of renal function and environmental exposures among a population at high risk of MeN before disease onset, providing critically important etiologic inferences. Chronic kidney disease of unknown origin is a global public health crisis, with concurrent epidemics in Sri Lanka, Egypt, and India, as well as throughout Central America. This study will inform international efforts to understand this phenomenon and reduce incidence.