India - Factors of CKDu in Uddanam Study (India-FOCUS)

总结 本提案介绍了组建一个经验丰富的多学科团队， 完成一项病因不明的慢性肾脏病（CKDu）的综合性现场流行病学研究， 印度南部乌丹纳姆的地方病流行区。这个印度焦点（印度-CKDu在Uddanam研究的因素） 该团队代表了肾脏疾病、流行病学、环境科学和项目领域的知名专家， 管理以及在低资源环境下实地工作的丰富经验。印度焦点团队， 他们有长期的合作关系，将有助于成功建立病例控制 一项纵向研究，包括400名CKDu参与者和800名对照者，每9 个月CKDu参与者的招募策略旨在仔细研究已知的 包括至少100个有2个或更多受影响个体的家庭的家族聚集性。招募的对照 将按年龄、性别、地点和职业与案件相匹配。研究参与者将仔细 表型分析包括详细的病史、暴露史、标准化的有效问卷， 详细的家族家谱临床检查本研究将收集生物标本（血液、尿液、毛发， 指甲），以测量肾功能、肾脏生物标志物 损伤和各种环境暴露的生物标志物（目标1a和1b）。一部分患者将接受 热应激的详细评价和肾小球滤过率的额外精确测量。我们将 还执行详细的环境样品（空气、水、土壤、硅胶带）收集协议， 平行生物样本收集，以促进环境暴露的目标和非目标分析（目的 2）。个体检测和环境样本的结果将适当返回至研究 参与者和社区在适当的时间点，以帮助了解有效的发展， 预防和干预措施（目标3）。将对研究受试者进行纵向随访， 将在对照组中识别CKDu病例。我们的研究旨在确定遗传学， 和基因-环境相互作用，代表了疾病进展的潜在病因和风险因素。 CKDu。社区参与将有助于制定可持续的干预措施， CKDU在这些社区。

Summary This proposal describes the formation of an experienced multidisciplinary team that is well equipped to complete a comprehensive field epidemiology study of chronic kidney disease of uncertain etiology (CKDu) in the endemic region of Uddanam in South India. This India-FOCUS (India- Factors of CKDu in Uddanam Study) team represents well-established experts in kidney disease, epidemiology environmental science, and project management as well as extensive experience in field work in low resource settings. The India-FOCUS team, who have long standing prior collaborations, will facilitate the successful establishment of a case control longitudinal study that includes 400 participants with CKDu and 800 controls with repeated visits every 9 months. The recruitment strategy for participants with CKDu is designed to allow for careful study of the known familial clustering by the inclusion of at least 100 families with 2 or more affected individuals. Recruited controls will be matched to cases by age, sex, location and occupation. Study participants will undergo careful phenotyping including a detailed medical history, exposure history, standardized validated questionnaires, detailed family pedigree charts, clinical examination. The study will collect biospecimens (blood, urine, hair, nails) from all participants at regular prespecified intervals to measure kidney function, biomarkers of kidney injury, and biomarkers of various environmental exposures (Aim 1a & 1b). A subset of patients will undergo detailed evaluation of heat stress and additional precise measurements of glomerular filtration rate. We will also implement a detailed environmental sample (air, water, soil, silicone bands) collection protocol that will parallel biospecimen collection to facilitate targeted and untargeted analyses of environmental exposures (Aim 2). The results of individual testing and environmental samples will be appropriately returned to the study participants and the community at appropriate time points to help inform the development of effective preventive and interventive measures (Aim 3). Study participants will be followed longitudinally and incident CKDu cases will be identified among the controls. Our study is designed to identify the genetics, exposome and gene-environmental interactions that represent the underlying etiology and risk factors for progression of CKDu. Community engagement will allow the development of sustainable interventions to reduce the burden of CKDu in these communities.