There is an epidemic of chronic kidney disease of unknown origin (CKDu) primarily affecting younger men in Central America, especially El Salvador and Nicaragua. The primary hypothesis has included heat stress and dehydration. Although medication usage is widely viewed as a likely contributor to kidney damage, the association with chronic kidney disease in Central America has not been fully explored. This study investigated medication usage, symptom presentation, and kidney function among 524 outdoor workers in agricultural and non-agricultural industries enrolled in the Mesoamerican Nephropathy Occupational Study (MANOS) led by Boston University researchers. An overview of the literature on the adverse effects of medication on renal function and thermoregulation, with a focus on medications considered in MANOS, was conducted. Medication usage and symptom presentation on both a short- and long-term timeframe were explored in relation to kidney function measured by estimated glomerular filtration rate. Long-term usage of NSAIDS and potassium supplements was significantly associated with kidney function. Neither short- or long-term uses of acetaminophen, the most commonly used medication, were associated with kidney function. While several self-reported health symptoms were significantly associated with lower kidney function in crude models, the associations’ significance levels lessened after adjusting for age, country, and industry. In contrast, symptoms of chistata (a local term for painful urination) and lower abdominal pain three months prior to data collection each significantly predicted higher kidney function. The results of this exploratory, cross-sectional study present an opportunity for further study on how medications and symptoms, related to both nephrotoxicity and heat stress, could be associated with kidney function.