Dietary phthalates and low-grade albuminuria in US children and adolescents.

BACKGROUND: Low-grade albuminuria is an indicator of endothelial dysfunction and is associated with an increased risk of cardiovascular disease. A graded level of exposure to bisphenol A was recently identified to be associated with increased risk of low-grade albuminuria in children and adults. Because bisphenol A and phthalates coexist as dietary contaminants, this study investigated whether exposure to phthalates is also associated with low-grade albuminuria.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data were examined from 667 children who participated in the 2009-2010 National Health and Nutrition Examination Survey and who had results for urinary phthalate metabolites and albumin excretion. Urinary albumin and creatinine concentrations were measured in a first morning specimen using a solid-phase fluorescent immunoassay and a Roche/Hitachi Modular P Chemistry Analyzer with an enzymatic method, respectively. Phthalate metabolites were analyzed in a separate spot urine sample from each participant, using high-performance liquid chromatography and tandem mass spectroscopy.

RESULTS: For each (roughly) 3-fold increase in metabolites of di-2-ethylhexylphthalate (a high molecular weight phthalate commonly found in foods), a 0.55 mg/g increase in albumin/creatinine ratio (ACR) was identified (P=0.02), whereas a 1.30-fold odds of a higher ACR quartile was also identified for each (roughly) 3-fold increase (P=0.02). Higher ACR was not identified in relationship to metabolites of lower molecular phthalates commonly found in lotions or shampoos, suggesting specificity.

CONCLUSIONS: Although reverse causation and unmeasured confounders represent alternative explanations, these findings, in conjunction with our earlier data on bisphenol A, indicate that a wide array of environmental toxins may adversely affect albuminuria and potentially increase the risk of cardiovascular disease. In view of the potential long-term health implications of ongoing exposure in this vulnerable subpopulation, our data support both further study and renewed regulatory efforts to limit exposure during childhood.