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Background: Associations between cadmium (Cd) and kidney function have been reported even at low levels of exposure in the general population. Recently, the causality of these associations has been questioned. Objectives: We examined associations between urinary Cd (U-Cd; a biomarker of exposure) and urinary proteins that are used as biomarkers of kidney effects, based on repeated short-term sampling in healthy subjects. Methods: Twenty-four hour urine samples were collected on 2 separate days at six fixed times from 30 healthy nonsmoking men and women (median age 39 years). We analyzed the samples (N = 354) for Cd (i.e., U-Cd) and two proteins used as kidney function biomarkers: urinary albumin (U-Alb) and alpha-1-microglobulin (U-A1M). Concentrations were adjusted for creatinine concentration or for specific gravity, and excretion rates (mass per hour) were calculated. Possible associations were assessed within each individual participant, and mean correlations and regressions were evaluated. Results: We found clear positive mean associations within individuals between the excretion of U-Cd [mean, 0.11 μg/g creatinine (range, 0.01–0.52 μg/g creatinine)] and both U-Alb and U-A1M. The associations were stronger for excretion rates and concentrations adjusted for specific gravity than for concentrations adjusted for creatinine. We also found significant positive associations of urinary flow with excretion of U-Cd, U-Alb, and U-A1M. Conclusions: Associations between short-term changes in U-Cd and markers of kidney function within individual nonsmoking study participants are unlikely to reflect effects of Cd toxicity. A more likely explanation is that these associations result from normal variation in renal function, including changes in urinary flow, that influence the urinary excretion of both Cd and proteins in the same direction. These effects of normal variability may result in overestimation of the adverse effects of Cd on kidney function at low-level Cd exposure. [ABSTRACT FROM AUTHOR]

BACKGROUND: Mercury is nephrotoxic and dental amalgam is a source of mercury exposure. METHODS: Children 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. RESULTS: There 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). CONCLUSIONS: The 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. [ABSTRACT FROM AUTHOR]