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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要中美洲肾病 (MeN) 是中美洲的一个主要原因，导致超过尽管对包括高温和危险因素在内的危险因素进行了十年的研究，但过去 20 年仍有 20,000 人死亡。随后的脱水、传染病、化学品暴露、药物和饮食，造成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。与世界其他地区的慢性肾病 (CKD) 不同，MeN 是一个重要的行业。其特点是发病早，患者在 20 多岁或更年轻的时候被诊断出来。我们波士顿大学的研究。自 2009 年以来在中美洲领导 MeN 研究的团队已经发现了肾损伤的证据该地区青少年肾功能下降，包括低 eGFR 患病率升高以及有证据表明过度滤过和肾脏损伤的尿液生物标志物，这两者都可能表明早期肾脏疾病。初步数据使我们认为生命早期接触肾毒性物质会导致肾损伤和肾功能下降，并且这些暴露会增加职业性工作后对 MeN 的易感性 2016 年（基线），我们的团队在尼加拉瓜招募并招收了 800 多名不同年龄段的青少年。 7-18岁，为儿童、青少年和年轻人的纵向队列奠定基础（ “NIÑOS”队列）在这个 R01 中，我们建议对这些 12-28 岁的年轻人进行跟踪。在研究开始时，为期 36 个月的研究目标是：1) 表征肾功能。尼加拉瓜青年期和青年期（eGFR 的年变化），该地区是 MeN 的高风险地区 2) 使用高通量蛋白质组分析（包括 >180 种蛋白质）来开发升高的预测生物标志物 eGFR 随时间的年化下降；3) 建立多种化学品之间的关联；和重金属与 eGFR 的年化变化，使用标准和“混合”分析技术 4) 使用硅胶腕带进行多化学暴露组分析，包括 >1500 种化学物质评估个人化学品暴露与肾功能之间的关联；以及 4) 评估使用个人热暴露监测来了解青少年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信息疾病发作前，MeN 高风险人群中的暴露情况，提供了极其重要的病因学信息原因不明的慢性肾病是一场全球性的公共卫生危机，并伴有流行病。这项研究将为斯里兰卡、埃及和印度以及整个中美洲提供信息。为了解这一现象并努力减少发生率。