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

NINOS 队列：CKDu 高风险地区的儿童肾脏健康

• 批准号: 10209651
• 负责人: Jessica H Leibler
• 金额: $ 63.03万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10209651
• 关键词: Acute; Address; Adolescence; Adolescent; Adolescent and Young Adult; Adult; Affect; Age; Age-Years; Agricultural Workers; Agriculture; Agrochemicals; Aromatic Polycyclic Hydrocarbons; Biological Markers; Boston; Cause of Death; Central America; Cessation of life; Characteristics; Chemical Exposure; Chemicals; Child; Chronic; Chronic Kidney Failure; Communicable Diseases; Country; Creatinine; Data; Dehydration; Diagnosis; Diet; Disease; Early Diagnosis; Egypt; Endocrine Disruptors; Enrollment; Environmental Exposure; Environmental and Occupational Exposure; Epidemic; Epidemiology; Etiology; Exposure to; Foundations; Funding; Future; Goals; Health; Heat Stress Disorders; Heavy Metals; Humidity; Incidence; Income; India; Individual; Industry; Injury to Kidney; International; Kidney; Kidney Diseases; Knowledge; Life; Light; Longitudinal cohort; Low Prevalence; Medical; Mesoamerican; Metals; Methodology; Methods; Monitor; Nicaragua; Occupational; Occupational Exposure; Occupations; Onset of illness; Outcome; Outcome Assessment; Pathology; Patients; Pesticides; Pharmaceutical Preparations; Population; Predisposition; Prevention; Proteins; Proteome; Proteomics; Public Health; Publishing; Recording of previous events; Renal function; Research; Risk Factors; Risk Reduction; Saccharum; Sampling; Serum; Silicones; Sri Lanka; Statistical Methods; Techniques; Temperature; Time; United States National Institutes of Health; Universities; Work; Youth; candidate marker; case control; cohort; design; early onset; experience; follow-up; high risk; innovation; longitudinal design; male; men; mortality; nephrotoxicity; novel; predictive marker; prevent; recruit; urinary; volatile organic compound; working men; young adult; young man

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.

项目摘要/摘要 中美洲肾病（MesoAmerican Nephropathy，MeN）是中美洲的主要死因， 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，包括热量和 随后的脱水、传染病、化学品暴露、药物和饮食、原因 毁灭性的疾病仍不清楚。大多数受影响的人是在农业部门工作的年轻男子。 工业，特别是甘蔗。与世界其他地区的慢性肾病（CKD）不同，MeN是 其特征在于早期发病，患者在20多岁或更年轻时被诊断。我们波士顿大学的研究 自2009年以来一直在中美洲领导MeN研究的团队已经确定了肾损伤的证据， 本区域青年人肾功能下降，包括低eGFR患病率升高， 肾损伤的高滤过和尿生物标志物，这两者都可能表明早期肾脏疾病。我们 初步数据使我们假设，生命早期，肾毒性暴露有助于肾损伤， 肾功能下降，这些暴露增加了职业性接触后对MeN的易感性， 生活中的暴露。2016年（基线），我们的团队在尼加拉瓜招募并招募了800多名青年，年龄 7-18年，为儿童、青少年和年轻人纵向队列奠定基础（ “NIH 3 OS”队列）。在本R 01中，我们建议对这些12-28岁的年轻人进行随访 在研究开始时，为期36个月。本研究的目的是：1）表征肾功能 在尼加拉瓜的青年和青年期（eGFR的年度变化），这是一个MeN的高风险地区; 2） 使用高通量蛋白质组学分析，包括>180种蛋白质，以开发升高的预测生物标志物 eGFR随时间的年化下降; 3）建立广谱化学物质之间的关联 和重金属与eGFR的年变化，使用标准和“混合物”分析技术; 4） 使用硅胶腕带进行多化学分析，包括>1500种化学品， 评估个人化学品暴露与肾功能之间的关系;以及4）评估 使用个人热暴露监测的青年人热暴露与肾功能之间的关联。 该项目将提供迄今为止最全面的肾功能和环境 在疾病发作前，在MeN高风险人群中暴露，提供了至关重要的病因学 推论不明原因的慢性肾脏病是一种全球公共卫生危机，同时存在流行病 在斯里兰卡、埃及和印度，以及整个中美洲。这项研究将为国际社会提供信息。 努力了解这一现象，减少发病率。