CKDu in Salvadoran and Nicaraguan Agricultural Communities

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PROJECT SUMMARY There is an epidemic of chronic kidney disease (CKD) in Central America, and the prevalence has been increasing over the past 20 years. El Salvador and Nicaragua have the highest overall mortality rates from kidney disease in the world, and CKD is the second leading cause of mortality among men of working age. In the US and Europe, CKD is common in older populations (age>60), affects men and women equally, and is primarily due to diabetes and hypertension. In contrast, CKD in certain regions of Central America disproportionately affects younger men and appears to be unrelated to diabetes or hypertension. Agricultural workers are the most affected, but the specific cause(s) remains unknown. Similar epidemics of chronic kidney disease of unknown etiology (CKDu) exist in Sri Lanka and India. The US National Institutes of Health is establishing a research consortium that will bring together a broad range of expertise and enable discovery science to understand the cause or causes of CKDu and disease progression. The Consortium will also work to identify potential therapeutic targets and public health intervention and will consist of a Scientific Data Coordinating Center, Field Epidemiology Sites, and a Renal Science Core. The Consortium will work together to finalize ethical epidemiology research designs, execute common strategies for biological sampling and environmental assessment, apply analytic strategies for collected samples and data, and disseminate results. This is a proposal for a Field Epidemiology Site in El Salvador and Nicaragua. Our aims are: (1) Develop study protocol with the CURE Consortium Steering Committee and SDCC to conduct longitudinal research on the causes and progression of CKDu; (2) Engage and consent up to 880 Salvadoran and Nicaraguan participants residing in well-documented high-risk CKDu communities into the CURE Consortium; (3) Conduct clinical assessments, collect biological and environmental samples, and administer questionnaires to determine disease status and risk factors for the examination of multiple hypotheses longitudinally for three years; (4) Engage in multi-directional and sustained communication among investigators and stakeholders locally and internationally, including communicating individual kidney function results to CURE participants, and overall study results to cohort participants, local partners, the scientific community, public health officials, and the general public. Our study team currently has a strong history together on this topic. Relevance Chronic kidney disease is estimated to be the 12th leading cause of death globally, with “hot spots” of kidney disease with no known causes. Our study of a high-risk population affected by chronic kidney disease in Central America (kidney disease “hot spots”) will contribute to scientific understanding of environmental contributors of disease susceptibility and severity with a particular focus on opportunities for prevention and treatment.