Environmental exposure assessment in the international prospective study of Chronic Kidney Disease of UnceRtain Etiology (CKDu) in Agricultural Communities (CURE) research consortium: Design and protocol development.

<h4>Background</h4>Chronic kidney disease of unknown etiology (CKDu) is a major health concern among outdoor manual workers in rural Central America and South Asia. The CURE study is a prospective longitudinal cohort designed to investigate CKDu's environmental risk factors through standardized exposure assessments, questionnaires, and biological and environmental sample collection.<h4>Methods</h4>This manuscript details the development of a standardized exposure assessment protocol within the CKDu CURE Consortium. The study recruits adults (18-45&nbsp;years) from CKDu hotspots across five countries, ensuring proportional representation across three eGFR categories (20-59, 60-89, ≥90&nbsp;mL/min/1.73m2) and excluding participants with diabetes or other known CKD causes. The CURE study is committed to promptly returning clinically and environmentally relevant test results to participants after analysis.<h4>Results</h4>Exposure assessment includes demographics, healthcare access, nephrotoxic medications, infectious pathogens, and agricultural work conditions (e.g., heat stress, hydration, diet, agrochemicals, toxicants). Biological and environmental samples (water, dust, soil, wristbands) are collected considering seasonal variations. Omics analyses, including metabolomics, will investigate environmental and biological interactions. Statistical analyses will assess relationships between exposures and CKDu onset or progression, incorporating environmental mixture analyses.<h4>Conclusion</h4>CURE will provide critical insights into CKDu risk factors, supporting future research and prevention strategies. A comprehensive exposure assessment will enhance understanding of environmental contributors, guiding interventions at individual, workplace, and community levels to mitigate CKDu's impact.