title: Confounders in the assessment of the renal effects associated with low-level urinary cadmium: an analysis in industrial workers.
abstract: BACKGROUND
  Associations 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.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  The 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 albumin
  
  
  CONCLUSIONS
  Associations 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.
authors.affiliation: Laboratory of Medical Toxicology, Faculty of Medicine, University Abou Bekr Belkaid, Tlemcen, Algeria.
authors.forename: Nahida
authors.initials: N
authors.lastname: Haddam
authors.forename: Sekkal
authors.initials: S
authors.lastname: Samira
authors.forename: Xavier
authors.initials: X
authors.lastname: Dumont
authors.forename: Abdesselem
authors.initials: A
authors.lastname: Taleb
authors.forename: Dominique
authors.initials: D
authors.lastname: Lison
authors.forename: Vincent
authors.initials: V
authors.lastname: Haufroid
authors.forename: Alfred
authors.initials: A
authors.lastname: Bernard
mesh_terms: D000328:Adult; D000419:Albuminuria; D000462:Algeria; D000510:Alpha-Globulins / Q000652:urine; D015415:Biomarkers / Q000652:urine*; D002104:Cadmium / Q000097:blood / Q000652:urine; D015986:Confounding Factors, Epidemiologic; D004231:Diuresis; D006801:Humans; D008297:Male; D008669:Metallurgy; D008875:Middle Aged; D016273:Occupational Exposure; D011507:Proteinuria / Q000139:chemically induced / Q000453:epidemiology* / Q000652:urine; D012177:Retinol-Binding Proteins / Q000652:urine; D012907:Smoking / Q000652:urine; D013783:Textile Industry; D015032:Zinc / Q000633:toxicity*
chemical_list: D000510:Alpha-Globulins; D015415:Biomarkers; D012177:Retinol-Binding Proteins; C016001:alpha-1-microglobulin; D002104:Cadmium; D015032:Zinc