Association of arsenic with kidney function in adolescents and young adults: Results from the National Health and Nutrition Examination Survey 2009-2012

Background: Long-term exposure to arsenic is a major public health concern. Emerging evidence suggests adverse health effects even at low levels of exposure. This study examined the association of arsenic exposure with estimated glomerular filtration rate (eGFR) and compared methods of adjustment for urinary dilution in a representative sample of U.S. adolescents and young adults. Methods: We performed a cross-sectional study of 1253 participants ages 12-30 years in the 2009-2012 National Health and Nutrition Examination Survey (NHANES) with available urinary arsenic and eGFR measures. Multivariable linear regression was used to model the association of urinary total arsenic and dimethylarsinate (DMA) with eGFR. Results: The median urinary total arsenic and DMA concentrations were 6.3μg/L (IQR 3.3-12.7μg/L) and 3.3μg/L (IQR 1.7-5.7μg/L), respectively. Median eGFR was 109mL/min/1.73m². Adjusting arsenic for urine concentration with urinary creatinine, eGFR was 4.0mL/min/1.73m² higher (95% confidence interval [CI] 1.0-7.1mL/min/1.73m²) and 4.3mL/min/1.73m² higher (95% CI 0.5-8.0mL/min/1.73m²) per log-unit increase in total arsenic and DMA, respectively. When using urine osmolality to adjust for urine concentration, a log-unit increase in total arsenic and DMA was associated with a 0.4mL/min/1.73m² (95% CI -1.8 to 1.1mL/min/1.73m²) and 0.01 (95% CI -1.9 to 1.9mL/min/1.73m²) lower eGFR, respectively. Conclusions: Discordant associations were observed between arsenic and eGFR levels depending on whether urinary creatinine or osmolality was used to adjust for urine concentration. Further study should be dedicated to validating the best approach to account for urinary dilution in research in toxicants, and this may have implications for all studies which examine urinary biomarkers.