Methodological considerations with the use of urine samples for assessment of mercury excretion and markers of renal damage.

OBJECTIVE: To provide recommendations for design and analysis of studies using urine specimens to evaluate renal function or mercury excretion in children. METHODS: An analysis of mercury, albumin, γ-glutamyl transpeptidase (γ-GT) and N-acetyl-ß-D-glucosaminidase (NAG) concentrations was carried out. RESULTS: Mercury concentration and creatinine-corrected renal markers were higher in daytime compared with overnight samples. Excretion rates increased with urinary flow rate. γ-GT and NAG concentrations decreased with storage time at -20°C. Differences by age, sex and race were noted. CONCLUSIONS: We recommend use of these creatinine-corrected markers and collection of timed overnight urine samples, stored at -70°C, with control for urinary flow rate, age, sex and race in statistical models.

Neuropsychological function in school-age children with low mercury exposures.

The EPA reference dose for methylmercury (MeHg) was established using data from populations with greater exposures than those typical of the US. Few data are available on potential adverse health effects at lower levels. We examined relationships between hair mercury (Hg) levels and neuropsychological outcomes in a population of US children. This study included data from 355 children ages 6-10 enrolled in the New England Children's Amalgam Trial. Data on total hair Hg levels, sociodemographic information and neuropsychological function were collected. We evaluated associations between hair Hg and neuropsychological test scores with linear regression methods and used generalized additive models to determine the shape of associations that departed from linearity. Models controlled for relevant covariates, including the potential beneficial effects of consuming fish. In adjusted models, we observed no significant linear relationships between hair Hg level and any test score. Significant departures from linearity were identified for WIAT Math Reasoning and WRAMVA Visual-Motor Composite scores. The association was positive for hair Hg levels below 0.5 microg/g and negative for levels between 0.5 and 1.0 microg/g. Overall, test scores of children with hair Hg levels 1.0 microg/g appeared to be lower than those of children with levels < 1.0 microg/g, but few children had levels in this upper range and these differences did not reach statistical significance. Hair Hg levels below 1.0 microg/g in US school-age children were not adversely related to neuropsychological function.

The influence of urinary flow rate in children on excretion of markers used for assessment of renal damage: albumin, gamma-glutamyl transpeptidase, N-acetyl-beta-D -glucosaminidase, and alpha1-microglobulin.

The aim of the present study was to examine the influence of urinary flow rate on markers of renal function in children. A sub-study of the New England Children's Amalgam Trial collected 82 pairs of urine samples from children aged 10-16 years: a timed overnight collection and a spot daytime sample collected the following day. These samples were analyzed for albumin, gamma-glutamyl transpeptidase (gamma-GT), N-acetyl-beta-D-glucosaminidase (NAG), alpha1-microglobulin (A1M), and creatinine concentration. Regression analysis was used to model the effect of urinary flow rate in the timed overnight samples. A paired t-test compared concentrations and creatinine-corrected renal markers between overnight and daytime samples. Albumin, gamma-GT, NAG, and A1M excretion rates increased significantly with urinary flow rate. Their corresponding creatinine-corrected markers did not vary significantly with urinary flow rate, but the creatinine-corrected excretions of albumin, gamma-GT, and NAG were significantly higher in daytime samples than in overnight samples, with the same (non-significant) trend for A1M. The influence of urinary flow rate on creatinine-corrected markers of renal function was markedly less than its influence on excretion rates. Therefore, the use of creatinine-corrected markers seems to be a good choice in practice, with the caveat that daytime and overnight samples are not comparable.