Associations between urinary dialkyl phosphate metabolites and cardiometabolic and kidney outcomes in U.S. children

Recent evidence links organophosphate pesticide exposure to cardiometabolic and kidney disorders in adults, but its impact in children remains poorly understood. This study evaluated associations between urinary dialkyl phosphate (DAP) metabolite concentrations and early markers of kidney and cardiovascular stress in children. A nationwide population sample of 2928 children less than 18 years of age from the 2015-2020 National Health and Nutrition Examination Survey (NHANES) was evaluated. The six DAP metabolites examined were dimethylphosphate (DMP), diethylphosphate (DEP), dimethylthiophosphate (DMTP), diethylthiophosphate (DETP), dimethyldithiophosphate (DMDTP) and diethyldithiophosphate (DEDTP). Clinical outcomes measured included both systolic and diastolic blood pressure indices, hypertensive status, microalbuminuria (albumin-to-creatinine ratio greater than 30 mg/g), and kidney hyperfiltration (estimated glomerular filtration rate greater than 135 mL/min/1.73m²). Multivariate linear and logistic regression models were used with adjustments made for age, gender, body mass index z-score, and poverty income ratio to evaluate the relationships among each of these clinical outcomes and levels of the metabolites. Statistical significance was set at p < 0.0167 due to the number of comparisons made. In adjusted models, higher urinary DAP metabolite concentrations were not significantly associated with systolic or diastolic blood pressure indices or hypertensive status (p > 0.05). However, higher DEDTP was significantly associated with both microalbuminuria (OR 1.290, 95% CI [1.051-1.583], p = 0.016) and kidney hyperfiltration (OR 2.348, 95% CI [1.658-3.324], p < 0.001). Additionally, higher DMDTP was significantly associated with hyperfiltration (OR 1.466, 95% CI [1.116-1.926], p = 0.007). In conclusion, higher urinary concentrations of specific DAP metabolites were associated with microalbuminuria and kidney hyperfiltration in U.S. children. These findings highlight the potential kidney effects of early-life organophosphate pesticide exposure and warrant further investigation into underlying mechanisms.