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

项目摘要：一种主要发生在年轻农业工人中的严重、不明原因的肾病流行病 至少二十年前在中美洲出现。从地理上讲，这一流行病现在从墨西哥蔓延到 向巴拿马传播，造成过早死亡，主要影响农村贫困社区。 中美洲肾病（Mesoamerican nephropathy，MeN）已导致超过20，000人死亡，但其病因仍然是一个谜， 传统的肾脏疾病危险因素不是MeN的危险因素。这种奇怪的疾病 既往被描述为无症状、隐匿性慢性肾病（CKD），病因不明， 迅速发展为终末期肾病和死亡。然而，Fischer博士和他的团队最近的一项研究表明， 巴布亚新几内亚农业工人群体揭示了CKD前急性临床综合征的证据， 首次描述了阿基和急性肾小管间质性肾炎。他们还观察到侵略性的 一个亚组（9%）的患者进展为CKD。关于急性脑神经病的新的、范式转变的证据表明， 这是一个早期但短暂的临床识别和干预的窗口。这也意味着早期的临床标志物 严重的疾病可能导致有针对性的干预措施。在这项提案中，菲舍尔博士将在这项研究的基础上， 在更广泛和更多样化的人群中对MeN进行临床研究。基于不断增长的 了解到MeN影响的社区比以前想象的更广泛，包括妇女和儿童，她 将开展以社区为基础的疾病监测，并建立第一个急性MEN社区队列 患者本研究的目的是验证急性MeN的临床病例定义，并描述 疾病的自然史，总体目标是增加我们对MeN的临床理解， 疾病监测和促进早期识别，诊断工作，临床干预，并有针对性地 未来的研究。拟议的研究是新颖的，解决了紧迫的公共卫生危机，它将 这是她职业发展的重要途径。费舍尔博士的战略和深思熟虑的计划将 通过指导性研究、正式课程、结构化教程和实践， 经验：（1）加强对热带疾病的临床认识;（2）保持多学科，长期， （3）用于复杂数据分析和解释的先进生物统计技术; （4）通过写作和演讲交流研究。总之，概述的研究， 导师，和职业提升将巩固知识，技能和信心，以提高和成为 R 01融资的竞争。福格蒂奖将提供保护的时间和资源，严格指导 培训期间和过渡到独立，因为她锻造长期，国际和多学科 合作，提高她的技能和领导能力，并成为专业准备发展一个 研究计划，重点是减少发病率和死亡率在中美洲和其他低资源 世界各地。

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.