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

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.