Investigation into the Epidemic of Unexplained Kidney Disease in Nicaragua: Understanding the Acute Clinical Scenario and Natural History of Disease in Mesoamerican Nephropathy.

尼加拉瓜不明原因肾脏病流行情况调查：了解中美洲肾病的急性临床情况和疾病自然史。

• 批准号: 9789713
• 负责人: Rebecca Susann Bryson Fischer
• 金额: $ 13.83万
• 依托单位: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-21 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9789713
• 关键词: Acute; Acute Disease; Acute Renal Failure with Renal Papillary Necrosis; Address; Affect; Agricultural Workers; Agriculture; Appearance; Award; Biometry; Biopsy; Central America; Cessation of life; Child; Chronic Disease; Chronic Kidney Failure; Chronic Phase; Clinical; Clinical Course of Disease; Clinical Management; Clinical Markers; Coin; Collaborations; Communities; Complement; Complex; Creatinine; Data; Data Analyses; Detection; Development Plans; Diagnosis; Diagnostic; Disease; Disease Progression; Disease Surveillance; Early identification; El Salvador; Emergent care; End stage renal failure; Environment; Epidemic; Epidemiology; Etiology; Foundations; Funding; Future; Geography; Goals; Guide prevention; Health; Health Priorities; Incidence; Individual; Inflammation; Infrastructure; Interdisciplinary Study; International; Interstitial Nephritis; Intervention; Investigation; Kidney; Kidney Diseases; Knowledge; Latin America; Lead; Leadership; Light; Longitudinal Studies; Mentors; Mentorship; Mesoamerican; Mexico; Morbidity - disease rate; Natural History; Nicaragua; Nicaraguan; Outcome; Panama; Pathway interactions; Patients; Physicians; Population; Population Heterogeneity; Premature Mortality; Preventive Intervention; Process; Public Health; Reporting; Research; Research Personnel; Resources; Risk Factors; Rural; Rural Community; Serum; Severity of illness; Structure; Syndrome; Techniques; Time; Training; Tropical Disease; Tubulointerstitial Nephritis; Woman; Writing; base; career; career development; clinical investigation; cohort; community setting; disease diagnosis; disease natural history; early onset; experience; global health; high risk; insight; men; mortality; multidisciplinary; novel; premature; prevent; programs; prospective; response; skills; study population; success; sugar

Project Summary: An epidemic of severe, unexplained kidney disease in mostly young agriculture workers emerged at least two decades ago in Central America. The epidemic now spans, geographically, from Mexico to Panama, causing premature mortality, predominantly affecting rural, impoverished communities. Mesoamerican nephropathy (MeN) has caused an excess of 20,000 deaths, yet its etiology remains a mystery, and traditional risk factors for kidney disease are not risk factors for MeN. The curious disease has been previously described as an asymptomatic, insidious chronic kidney disease (CKD) of unknown etiology that progresses rapidly to end stage renal disease and death. However, recent studies by Dr. Fischer and team in a Nicaraguan agriculture worker population reveal evidence of an acute clinical syndrome preceding CKD and described for the first time AKI and acute tubulointerstitial nephritis in MeN. They also observed aggressive progression to CKD in a subset (9%) of patients. The new, paradigm-shifting evidence about acute MeN suggests an early, yet brief, window for clinical recognition and intervention. It also implies that early clinical markers for severe disease could lead to targeted interventions. In this proposal, Dr. Fischer will build on this research by leading a clinical investigation into MeN in a broader and more diverse populations. Based on a growing understanding that MeN affects a broader community, including women children, than previously thought, she will conduct community-based disease surveillance and establish the first community cohort of acute MeN patients. The aims of the research are to validate a clinical case definition of acute MeN and describe the natural history of disease with the overall goal of increasing our clinical understanding of MeN to enable disease surveillance and to facilitate early identification, diagnostic work-up, clinical intervention, and targeted future research. The proposed research is novel and addresses and urgent public health crisis, it and will serve as an important avenue for her career development. Dr. Fischer's strategic and thoughtful plan will address four career objectives through mentored research, formal courses, structured tutorials, and practical experiences: (1) enhanced clinical understanding of tropical disease; (2) maintaining multidisciplinary, long- distance collaborations; (3) advanced biostatistical techniques for complex data analysis and interpretation; and (4) communicating research through writing and presentations. Together, the outlined research, mentorship, and career enhancement will fortify the knowledge, skills, and confidence to advance and become competitive for R01 funding. The Fogarty award will afford protected time and resources for a rigorous mentored training period and transition to independence, as she forges long-term, international and multidisciplinary collaborations, advances her skill-set and leadership abilities, and becomes professionally poised to develop a research program that focus on reducing morbidity and mortality in Central America and other low-resource regions of the world.

项目摘要：主要是年轻农业工人的严重，无法解释的肾脏疾病流行 至少在二十年前出现在中美洲。现在，从墨西哥那里跨越了流行病 到巴拿马，导致过早死亡，主要影响农村，贫困的社区。 中美洲肾病（男性）造成超过20,000人死亡，但其病因仍然是一个谜， 肾脏疾病的传统危险因素不是男性的危险因素。好奇的疾病已经 先前被描述为一种无症状，阴险的慢性肾脏疾病（CKD），未知病因 迅速发展到终止阶段肾脏疾病和死亡。但是，Fischer博士和团队的最新研究 尼加拉瓜农业人员人口揭示了CKD前急性临床综合征的证据， 男性首次描述了AKI和急性微管间质肾炎。他们还观察到了侵略性 子群（9％）患者的CKD进展。有关急性男人的新的，范式转移的证据表明 临床识别和干预的早期但简短的窗口。这也暗示着早期的临床标记 严重的疾病可能导致针对性的干预措施。在此提案中，菲舍尔博士将在这项研究的基础上建立 领导对更广泛，更多样化的人群中男性的临床研究。基于成长 了解男人比以前想象的那样影响着一个更广泛的社区，包括儿童，她 将进行基于社区的疾病监测，并建立第一个急性男性的社区队列 患者。该研究的目的是验证急性男性的临床病例定义，并描述 疾病的自然史，其总体目标是增加我们对男性的临床理解以实现 疾病监测并促进早期识别，诊断检查，临床干预和目标 未来的研究。拟议的研究是新颖的，解决的以及紧急的公共卫生危机，IT并将 作为她职业发展的重要途径。菲舍尔博士的战略和周到的计划将 通过指导的研究，正式课程，结构化教程和实用性来解决四个职业目标 经验：（1）增强对热带疾病的临床理解； （2）维持多学科的长期 距离协作； （3）用于复杂数据分析和解释的高级生物统计技术； （4）通过写作和演讲进行研究。概述的研究一起 指导和提高职业将加强知识，技能和信心 R01资金的竞争力。 Fogarty奖将为严格的指导提供受保护的时间和资源 培训期和向独立过渡，因为她长期，国际和多学科锻炼 合作，提高她的技能和领导能力，并成为专业准备发展的 研究计划的重点是降低中美洲和其他低资源的发病率和死亡率 世界地区。