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

摘要 本提案描述了组建一支经验丰富的多学科团队，该团队装备精良，能够 完成不明原因慢性肾脏病(CKDu)的全面现场流行病学研究 印度南部乌达纳姆的一个流行地区。《聚焦印度》(印度--Uddanam研究中的CKDu因素) 团队代表肾脏疾病、流行病学、环境科学和项目方面的知名专家 在资源匮乏的情况下，有丰富的管理经验和丰富的实地工作经验。聚焦印度的团队， 他们有长期的合作关系，将有助于成功地建立病例控制 一项纵向研究，包括400名CKDu患者和800名对照组，每隔9天重复访问一次 月份。CKDU参与者的招募策略旨在允许仔细研究已知的 家庭聚集性，包括至少100个家庭和2个或更多受影响的个人。招募的控制组 将按年龄、性别、地点和职业与病例匹配。研究参与者将仔细地接受 表型鉴定包括详细的病史、接触史、标准化的有效问卷、 详细的家族谱系图，临床检查。这项研究将收集生物标本(血液、尿液、头发、 指甲)，以定期预先指定的时间间隔测量肾功能、肾脏的生物标志物 伤害和各种环境暴露的生物标记物(目标1a和1b)。一部分患者将接受 对热应激的详细评估和对肾小球滤过率的额外精确测量。我们会 还执行详细的环境样本(空气、水、土壤、硅胶胶带)收集协议，以 并行生物检疫收集，以促进环境暴露的定向和非定向分析(AIM 2)。个别测试和环境样本的结果将适当地返回研究 参与者和社会人士在适当的时间点帮助通知有效的发展 预防和干预措施(目标3)。研究参与者将被纵向跟踪和事件 CKDu病例将在控制组中确定。我们的研究旨在确定基因，曝光组 以及基因-环境相互作用，代表了疾病进展的潜在病因和风险因素 CKDu。社区参与将允许制定可持续的干预措施，以减轻 这些社区中的CKDu。

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.