Project Summary/Abstract An epidemic of unexplained kidney disease in young agriculture workers appeared at least two decades ago in Central America. The epidemic of chronic kidney disease of unknown origin (CKDu) causes premature mortality and predominantly affects rural communities. CKDu is not caused by traditional risk factors such as diabetes or hypertension. The hypothesis for the proposed study is that exposure to high concentrations of airborne contaminants will be associated with kidney injury in females at-risk for CKDu in Guatemala. Nearly all research to date has focused on males, neglecting preliminary data showing that females working in agriculture and living in agricultural communities are also affected by CKDu. Additionally, studies to date have largely overlooked consideration of air pollutants as contributors to CKDu etiology. In this proposal, we will characterize in (Aim months repeat airborne exposure to particulate matter (PM) and metals over a 24-hour monitoring period 50 female sugarcane workers and in 50 female community members not involved in the sugarcane sector 1). The 24-hour monitoring period will occur at two time points for each participant approximately 3 apart. In addition,we will conduct a quantitative screen of 125 organic chemicals via a silicone wristband worn by the participants over a 7-day period (Aim 2). We will evaluate the relationships between individual exposures (PM, metals, and organic chemicals) and a kidney biomarker of effect (creatinine) (Aims 1 and 2). The overall goal of the study is to increase understanding of risk factors for CKDu in women in order to facilitate targeted future research and prevention strategies. The proposed research is novel, addresses a research knowledge gap in an understudied, vulnerable population, and will serve as an important avenue for Dr. Butler-Dawson's career development. Dr. Butler-Dawson's plan will address four career objectives through mentored research, formal courses, structured tutorials, and practical experiences: (1) to increase my skill-set in environmental epidemiology; (2) to develop skills in exposure science; (3) to gain experience in advanced biostatistical techniques for multi- level modeling and interpretation; and (4) to effectively communicate scientific concepts and further develop leadership skills. Her mentor, Dr. John Adgate, Professor and Chair in the Department of Environmental and Occupational Health, as well as her committee members, Drs. Lee Newman (occupational health and safety practitioner), Katherine James (environmental epidemiologist), Richard Johnson (nephrologist), and James Crooks (biostatistician) will provide her with strong mentorship throughout this project. The outlined K01 award will provide protected time and resources for a rigorous training and mentoring period and subsequent transition to a successful independent researcher in environmental epidemiology.