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.