ABSTRACT Chronic kidney disease of uncertain etiology (CKDu) has reached epidemic proportions in Costa Rica’s Guanacaste province (Chorotega region), where it has become a leading cause of premature death. CKDu has a high burden among young, male agricultural workers, but women and children are also affected, and its causes remain largely unknown. In response to the RFA for Field Epidemiology Sites for the Chronic Kidney Diseases of UnceRtain Etiology in Agricultural Communities Research Consortium (CURE Consortium), we propose to recruit, enroll and follow 400 participants with evidence of CKDu and 400 control participants for comprehensive assessments of individual risk factors and contextual exposures for CKDu. We propose an Epidemiology Field Center in Liberia, Chorotega region, as part of a collaboration among the University of North Carolina at Chapel Hill, the University of Costa Rica and local nephrologists in the Chorotega region. Our study design includes a large case-control study with nested substudies and state-of-the art exposure assessment methods to identify risk factors and cause(s) of CKDu. We will conduct clinical assessments and collect extensive biological and environmental/occupational samples and data. In addition to analysis of a wide range of self-reported lifestyle/demographic, environmental, and occupational factors and environmental measurements in the case-control study, we will conduct 1) a nested family study to assess familial aggregation/genetic susceptibility; 2) a prospective study among controls of serial targeted and non-targeted contemporary environmental/occupational chemical exposures (exposomics) measured in urine and drinking water in relation to measures of acute kidney injury (AKI) and new-onset CKDu; and 3) a prospective field study among a representative sample of controls employed in agriculture and construction to investigate seasonal workplace exposures through repeat measures of targeted and non-targeted chemical exposures (exposomics, including but not limited to pesticide, metals, and combustion products), assessed in urine and via silicone wristband samplers, in relation to measures of heat stress-related AKI. We propose to assemble a resource of sufficient breadth, depth and size to permit informative assessments of a wide range of risk factors, including environmental/occupational exposures and health contexts, with sufficient power to identify one or more causes of CKDu that could be targeted for prevention, intervention or policy.

PROJECT NARRATIVE The proposed Field Epidemiology Site (FES) located in the Chorotega region in Costa Rica will recruit, enroll and follow participants for the CURE Consortium and perform comprehensive assessments of risk factors, environmental exposures and health contexts, allowing to identify one or more causes for CKDu that could be targeted for prevention, intervention or policy.