Abstract
BackgroundAssociations of proteinuria with low-level urinary cadmium (Cd) are currently interpreted as the sign of renal dysfunction induced by Cd. Few studies have considered the possibility that these associations might be non causal and arise from confounding by factors influencing the renal excretion of Cd and proteins.MethodsWe examined 184 healthy male workers (mean age, 39.5 years) from a zinc smelter (n = 132) or a blanket factory (n = 52). We measured the concentrations of Cd in blood (B-Cd) and the urinary excretion of Cd (U-Cd), retinol-binding protein (RBP), protein HC and albumin. Associations between biomarkers of metal exposure and urinary proteins were assessed by simple and multiple regression analyses.ResultsThe medians (interquartile range) of B-Cd (μg/l) and U-Cd (μg/g creatinine) were 0.80 (0.45-1.16) and 0.70 (0.40-1.3) in smelter workers and 0.66 (0.47-0.87) and 0.55 (0.40-0.90) in blanket factory workers, respectively. Occupation had no influence on these values, which varied mainly with smoking habits. In univariate analysis, concentrations of RBP and protein HC in urine were significantly correlated with both U-Cd and B-Cd but these associations were substantially weakened by the adjustment for current smoking and the residual influence of diuresis after correction for urinary creatinine. Albumin in urine did not correlate with B-Cd but was consistently associated with U-Cd through a relationship, which was unaffected by smoking or diuresis. Further analyses showed that RBP and albumin in urine mutually distort their associations with U-Cd and that the relationship between RBP and Cd in urine was almost the replicate of that linking RBP to albuminConclusionsAssociations between proteinuria and low-level urinary Cd should be interpreted with caution as they appear to be largely driven by diuresis, current smoking and probably also the co-excretion of Cd with plasma proteins.
Highlights
Cadmium (Cd) is a widespread pollutant that accumulates in the soil, the food chain and in the human body
The corresponding threshold level for urinary Cd, an indicator of the Cd body burden in industrial workers, has been estimated at 10 μg/creatinine [5,6]. This urinary excretion of Cd (U-Cd) threshold level has been confirmed in a recent study, which estimated the U-Cd benchmark dose for the LMW proteinuria induced by Cd at 12-13 μg/g creatinine with a lower confidence interval limit of about 5-6 μg/g creatinine [7]
That the urinary excretion of Cd was consistently associated with the excretion of albumin through a relationship, which was unaffected by diuresis, age or smoking
Summary
Cadmium (Cd) is a widespread pollutant that accumulates in the soil, the food chain and in the human body. Studies among industrial workers and populations living in heavily polluted areas have clearly shown that Cd causes tubular dysfunction in a dose-dependent manner, the tubular proteinuria developing only when the renal accumulation has reached a critical threshold. The corresponding threshold level for urinary Cd, an indicator of the Cd body burden in industrial workers, has been estimated at 10 μg/creatinine [5,6]. This U-Cd threshold level has been confirmed in a recent study, which estimated the U-Cd benchmark dose for the LMW proteinuria induced by Cd at 12-13 μg/g creatinine with a lower confidence interval limit of about 5-6 μg/g creatinine [7]. Few studies have considered the possibility that these associations might be non causal and arise from confounding by factors influencing the renal excretion of Cd and proteins
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