Confounders in the assessment of the renal effects associated with low-level urinary cadmium: an analysis in industrial workers

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.

Novel urinary biomarkers and their association with urinary heavy metals in chronic kidney disease of unknown aetiology in Sri Lanka: a pilot study

“…In more recent studies conducted in the general population, urinary Cd levels below the accepted threshold of 2µg/g creatinine have been shown to be associated with kidney disease and albuminuria [25]. Haddam et al concluded that these associations could be due to influence of confounders such as diuresis, smoking or co-excretion with urinary proteins rather than direct effect of Cd [26]. The mean UCd concentration in CKDu patients and controls in our study is even below these threshold limits.…”

Inverse association between intelligence quotient and urinary retinol binding protein in Chinese school-age children with low blood lead levels: Results from a cross-sectional investigation

“…The level of urinary retinol-binding protein (RBP) can be estimated as a significant index of renal tubular injury (Hu et al, 2012), which was used to evaluate the effect of Cd on renal function (Haddam et al, 2011). In the present study, we found a strong association between RBP and IQ.…”

“…However, few studies have assessed the effects of joint exposure to heavy metals on IQ or health (Bellinger, 2008a). Retinol binding protein (RBP) in urine is usually used to evaluate the effect of cadmium (Cd) on kidney function (Haddam et al, 2011). However, urinary RBP was found to be significantly associated with blood Pb (Bernard et al, 1995), which prompted us to measure RBP in order to probe the complex relationships among heavy metals.…”

Correlation of Cadmium Intake from Water and Biomarkers in Resident Living Around Namobintang Dumpsite

“…It has been reported that one cigarette contains 1 to 2 μg of Cd [8]. According to the study of Haddam et al [9], the levels of Cd in urine were higher in current smokers than non smokers (1 vs 0.48 μg/gCr) among between Zinc smelter workers in Algeria. The increased excretion of urinary low molecular weight proteins such as β 2 -MG is most probably due to the renal toxicity of tobacco smoke.…”