Biomarkers of kidney integrity in children and adolescents with dental amalgam mercury exposure: findings from the Casa Pia children's amalgam trial.

Mercury is toxic to the kidney, and dental amalgam is a source of mercury exposure. Few studies have evaluated the effects of dental amalgam on kidney function in a longitudinal context in children. Here, we evaluated urinary concentrations of glutathione S-transferases (GSTs) alpha and pi as biomarkers of renal proximal and distal tubular integrity, respectively, and albumin as a biomarker of glomerular integrity in children and adolescents 8-18 years of age over a 7-year course of dental amalgam treatment. Five hundred seven children, 8-12 years of age at baseline, participated in a clinical trial to evaluate the neurobehavioral and renal effects of dental amalgam in children. Subjects were randomized to either dental amalgam or resin composite treatments. Urinary GSTs alpha and pi, albumin, and creatinine concentrations were measured at baseline and annually in all subjects. Results were evaluated using linear regression analysis. GST-alpha concentrations were similar between treatment groups and in each sex and race (white vs. non-white) group in each follow-up year. GST-pi levels tended upward over the course of follow-up by four- to six-fold. This increase was seen in all groups irrespective of the treatment, race, or gender. Females had GST-pi levels approximately twice those of males at all ages. Albumin concentrations were constant throughout the follow-up period and did not differ by treatment, although females had 39% higher albumin levels than males. Additionally, we found no significant effects of amalgam treatment on the proportion of children with microalbuminuria (>30 mg/g creatinine). These findings are relevant within the context of children's health risk assessment as relates to the safety of mercury exposure from dental amalgam on kidney function. These data also provide normative values for sensitive indices of renal functional integrity that may serve in the evaluation of children and adolescents with renal disorders.