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BACKGROUND: Mesoamerican nephropathy is a public health crisis in young men in Central America. The disease does not share risk factors of chronic kidney disease (i.e. diabetes and hypertension) commonly seen in the U.S. Exposure to nephrotoxic agrochemicals is a hypothesized contributor to disease, but individual-level exposure measurements are lacking, as are analyses of exposures and outcomes.OBJECTIVES: Measure associations between urinary pesticides and kidney function within the Mesoamerican Nephropathy Occupational Study, a cohort of male workers aged 18-45 in Nicaragua and El Salvador.METHODS: Urine from 285 participants at two timepoints, enrollment and one year later, was analyzed for glyphosate and AMPA using HPLC-MS/MS. Urine of 50 participants from enrollment was also analyzed for four organophosphate, two phenoxy acid, and five pyrethroid pesticide metabolites using HPLC-MS/MS. We estimated associations between urinary pesticides and agrochemical jobs and estimated glomerular filtration rate (eGFR) cross-sectionally, over one year, and over the study period (two-and-a-half years in Nicaragua; three years in El Salvador).RESULTS: Higher urine glyphosate levels were associated with lower eGFR over one year, with significant associations for the lower exposure group (≤median): -4.0 mL/min/1.73 m (95% CI: -7.2, -0.87 mL/min/1.73 m). However, participants with detectable urine glyphosate at both time points had lower odds of at least a 10% decline in eGFR decline over the study period (OR 0.33; 95% CI: 0.16, 0.65). The protective effect in our longer-term model may reflect healthy worker bias. Meanwhile, having an agrochemical job was significantly associated with higher odds of at least a 20% decline in eGFR over the study period (OR 1.7; 95% CI: 1.3, 2.3).SIGNIFICANCE: Urine pesticide levels were not consistently associated with reduced kidney function. 59 Having an agrochemical job was a predictor of kidney function decline. Other agricultural exposures, either individually or in combination with pesticides, may drive disease risks observed in this population.IMPACT: We evaluated urine concentrations of pesticides, including glyphosate, in a cohort of male workers in five industries (brickmaking, road construction, corn, plantain, and sugarcane) in El Salvador and Nicaragua, an area with endemic Mesoamerican nephropathy and where pesticide biomonitoring data in general is lacking. We found weak and limited evidence of associations between urinary glyphosate or other pesticide levels and change in kidney function. However, we observed a significant positive association between having an agrochemical job and kidney decline over the study period.