Particulate exposure and kidney health

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Project Summary/Abstract The overarching goals of this proposal are to contribute to the understanding of the causes, mechanisms, and potential strategies for prevention of the international epidemic of chronickidney disease of unknown origin (CKDu). Our central hypothesis is that exposure to high concentrations of air contaminants will be associated with acute kidney injury in agricultural workers and that heat stress and dehydration will produce adverse effects on kidney biomarkers. We further hypothesize that this damage occurs through a vasopressin-mediated injury pathway. Access to a population of sugarcane workers in cooperation with a major Guatemalan agribusiness will allow for a study that characterizes sugarcane worker exposure to particulate matter (PM) and it constituents (silica, glyphosate, and metals) in conjunction with personal factors, including dehydration and heat stress. We will examine the individual contribution of air contaminant exposure, as well as the combined contribution of exposure and personal risk factors, on kidney dysfunction. In addition, we will investigate the mechanistic role of the vasopressin pathway to pathogenesis of CKDu. This exposure pathway development relationship dehydration investigate an unexplored identify may workers at risk for the of kidney dysfunction by conducting a robust personal exposure assessment, b) evaluate the between exposure(s) and acute kidney injury, and c) examine underlying mechanisms by which and heat stress contribute to increased risk of CKDu in conjunction with nephrotoxicant exposures. research will: a) to inhalation exposures that place agricultural To metals, on evaluate identify address this hypothesis, three aims are proposed: Aim 1 focuses on characterizing exposure to PM, silica, and glyphosate in Guatemalan sugarcane workers and examining the impact of meteorological factors personal exposure. We will use prospective, quantitative personal measurements in workers. Aim 2 will the relationship between occupational air contaminant exposure and kidney biomarkers of effect to workers withincreased risk of cross-shift worsening renal function and inflammation. Aim 3 will evaluate the potential mechanism by which environmental and individual risk factors induce kidney injury. The proposed panel study will collect repeat respirable PM personal air samples across two 6-month harvest seasons in two groups of 60 clinical Guatemala. data and Next, biological workers, totaling 120 workers samples from participants at . First, the we will collect baseline questionnaire and time of hire at a sugarcane plantation in we will collect personal air measurements for each participant during the entire work shift to estimate daily airborne exposure glyphosate, and heavy metals, as well as urine and blood biomarkers pre- and post-shift t three time points for each worker during the two seasons. to silica, a Resultsof this research will lead tolarge-scale intervention trials that will help to prevent CKDu by targeting potential therapeutic approaches for vulnerable populations that can be disseminated internationally.