Abstract
BACKGROUND: Agricultural workers are consistently exposed to elevated heat exposures and vulnerable to acute kidney injury. The underlying pathophysiology and detailed molecular mechanisms of AKI among agricultural workers, and the disproportionate burden of HRI and heat stress exposure are not well understood, especially at the level of cellular metabolism. OBJECTIVE: The aim of this study was to examine the impact of heat exposures on renal biomarkers and on the human metabolome via untargeted high-resolution metabolomics among agricultural and non-agricultural workers. METHODS: Blood and urine samples were collected pre- and post-work shift from 63 agricultural workers and 27 non- agricultural workers. We evaluated pre- and post-work shift renal biomarkers and completed untargeted metabolomics using high-resolution mass spectrometry with liquid chromatography. Metabolome-wide association studies (MWAS) models identified the metabolic features differentially expressed between agricultural workers and non-agricultural workers. RESULTS: Median values of pre-shift creatinine and osteopontin (p < 0.05) were higher for agricultural workers than non-agricultural workers. Metabolic pathway enrichment analyses revealed 27 diverse pathways differed between agricultural workers and non-agricultural workers (p < 0.05) including TCA cycle and urea cycle, carbohydrate metabolism, histidine metabolism and evidence for altered microbiome shikimate pathway. CONCLUSION: This is the first investigation on the metabolic pathways that are affected among agricultural workers who are exposed to heat compared to non-heat exposed workers. This study shows extensive responses of central metabolic systems to heat exposures that impact human health.