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: 10552058
• 负责人: Jessica H Leibler
• 金额: $ 58.25万
• 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/10552058
• 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; Early identification; 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; 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; 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; Early identification; 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; 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（男性）是中美洲死亡的主要原因，导致多数超过 过去20年中有20,000人死亡。尽管研究了数十年的风险因素，包括热量和 随后的脱水，传染病，化学暴露，药物和饮食，原因是 毁灭性疾病尚不清楚。大多数受影响的人是从事农业工作的年轻人 行业，尤其​​是甘蔗。与世界其他地区的慢性肾脏病（CKD）不同，男性是 以早期发作为特征，患者在20年代或以上被诊断出。我们的波士顿大学研究 自2009年以来一直领导中美洲研究的团队已经确定了肾脏损伤和 该地区青年的肾功能下降，包括较低的EGFR患病率和证据 肾脏损伤的过滤和尿生物标志物，这两者都可能表明早期肾脏疾病。我们的 初步数据使我们假设早期生活，肾毒性暴露会导致肾脏损伤和 肾功能下降，这些暴露会增加对占领后男性的敏感性 以后的生活。 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 7 - 18年，为纵向的儿童，青少年和年轻人奠定了基础（ “Niños”队列）。在此R01中，我们建议与这些年轻人进行跟进，他们将年满12-28岁 在研究开始时，持续了36个月。这项研究的目标是：1）表征肾功能 在尼加拉瓜的青年和成年期（EGFR年度变化）期间，男性高风险地区； 2） 使用高通量蛋白质组学分析，包括> 180种蛋白质，开发升高的预测生物标志物 随着时间的流逝，EGFR的年化下降； 3）建立众多化学品之间的关联 以及使用标准和“混合”分析技术的EGFR年度变化的重金属； 4） 使用硅酮腕带进行多物质的释放组分析，包括> 1500种化学物质 评估个人化学暴露与肾功能之间的关联； 4）评估 使用个人热暴露监测，在青年人中接触热量与肾功能之间的关联。 该项目将提供截至肾功能和环境的最全面的帐户 在疾病发作前处于高风险的人群中的暴露，提供至关重要的病因 推论。未知来源的慢性肾脏疾病是全球公共卫生危机，并发流行病 在斯里兰卡，埃及和印度以及整个中美洲。这项研究将告知国际 努力理解这种现象并降低发生率。