Renal Effects of Dental Amalgam in Children: The New England Children’s Amalgam Trial

Abstract

BackgroundMercury is nephrotoxic and dental amalgam is a source of mercury exposure.MethodsChildren 6–10 years of age (n = 534) with two or more posterior teeth with caries but no prior amalgam restorations, were randomized to one of two treatments—amalgam or resin composite (white fillings)—used for caries treatment during 5 years of follow-up. The primary outcome was change in IQ, but important secondary outcomes were effects on markers of glomerular and tubular kidney function: urinary excretion of albumin, alpha-1-microglobulin (A1M), γ-glutamyl transpeptidase (γ-GT), and N-acetyl-β-d-glucosaminidase (NAG). These markers were measured on several occasions during the trial, together with urinary mercury and covariates. We evaluated the results using repeated-measures analyses.ResultsThere were no significant differences between treatment groups in average levels of renal biomarkers, nor significant effects of number of dental amalgams on these markers. There was, however, a significantly increased prevalence of microalbuminuria (MA) among children in the amalgam group in years 3–5 (adjusted odds ratio 1.8; 95% confidence interval, 1.1–2.9). Most of these cases are likely to be temporary MA, but 10 children in the amalgam group had MA in both years 3 and 5, versus 2 children in the composite group (p = 0.04). There were no differences in the occurrence of high levels of renal tubular markers (A1M, γ-GT, or NAG).ConclusionsThe increase in MA may be a random finding, but should be tested further. The results did not support recent findings in an observational study of an effect of low-level mercury on tubular biomarkers in children.

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

“…The findings suggest no deleterious effects of mercury exposure from dental amalgam on either proximal or distal tubule cellular integrity, as indicated by the lack of significant differences in either GST α or π, respectively, between amalgam and composite groups over a prolonged course of treatment. While other measures of tubular integrity were not evaluated in this study, these findings are consistent with those of Barregard et al, (2008) who reported no changes in alpha-1-microglobulin, γ-glutamyl transpeptidase or N -acetyl-β-D-glucosaminidase in children participating in the New England Children’s Amalgam Trial (NECAT), conducted concurrently with the present study. Comparable findings by de Burbure et al, (2003) suggested that no renal lesions appear to occur in children with mean urinary Hg levels up to 13.4 μg/g creatinine and a maximum of 25 μg/g creatinine.…”

“…Similar findings have been reported by other investigators who evaluated urinary albumin excretion in relation to amalgam mercury exposure among healthy human subjects (Herrström et al, 1995; Langworth et al, 1997; Sandborgh-Englund et al, 1996). In contrast, Barregard et al, (2008) reported a significantly higher proportion of children with microalbuminuria (i.e., > 30 mg/g creatinine) among those receiving dental amalgam treatment compared with those receiving composite resin fillings during the 3 rd and 5 th years of follow-up in the NECAT study. Using the same metrics (creatinine-adjusted albumin >30 mg/gm) reported therein, in addition to comparison of median urinary albumin values previously reported (DeRouen et al, 2006), our analyses revealed no significant effects of amalgam treatment on the proportion of children with microalbuminuria in the present study.…”

Non-drug-induced nephrotoxicity

“…In 2008 the results of a specific pediatric trial, the New England Children's Amalgam Trial, were published: 534 children 6-10 years of age with two or more posterior teeth caries but with no prior amalgam restorations were randomly chosen to be given amalgam or resin composites. After a 5-year follow-up period, there were no significant differences between groups for renal tubular biomarkers, but there was a significantly increased prevalence of microalbuminuria among children in the amalgam group (adjusted odds ratio 1.8, 95% confidence interval 1.1-2.9) [28].…”

Abstracts

“…In the NECAT study, there was no difference in mean albumin excretion between treatment groups, nor where there any associations with amalgam or U-Hg for the renal tubular markers γ-glutamyl transferase (γ-GT), alpha-1-microglobulin (A1M) or N-acetylglucose-aminidase (NAG) (Barregard et al 2008).…”