title: Associations of urinary cadmium with age and urinary proteins: further evidence of physiological variations unrelated to metal accumulation and toxicity.
abstract: BACKGROUND
  The current risk assessment for environmental cadmium (Cd) largely relies on the assumption that urinary Cd (U-Cd) is a reliable biomarker of the Cd body burden. Recent studies have questioned the validity of this assumption.
  
  
  OBJECTIVE
  We studied the lifetime trend of U-Cd as a function of diuresis, gender, smoking status, and protein tubular reabsorption. We also analyzed the associations between U-Cd and urinary proteins.
  
  
  METHODS
  Cd, retinol-binding protein, and albumin were measured in the urine of six cohorts of the general population of Belgium, with a mean age ranging from 5.7 to 88.1 years (n = 1,567). Variations of U-Cd with age were modeled using natural cubic splines.
  
  
  RESULTS
  In both genders, U-Cd decreased to a minimum (~ 0.20 μg/L) at the end of adolescence, then increased until 60-70 years of age (~ 0.60 μg/L in never-smokers) before leveling off or decreasing. When U-Cd was expressed in micrograms per gram of creatinine, these variations were amplified (minimum, 0.15 µg/g creatinine; maximum, 0.70 µg/g creatinine) and much higher U-Cd values were observed in women. We observed no difference in U-Cd levels between never-smokers and former smokers, and the difference with current smokers did not increase over time. Lifetime curves of U-Cd were higher with increasing urinary retinol-binding protein or albumin, a consequence of the coexcretion of Cd with proteins.
  
  
  CONCLUSIONS
  At low Cd exposure levels, U-Cd and age are associated through nonlinear and nonmonotonic relationships that appear to be driven mainly by recent Cd intake and physiological variations in the excretion of creatinine and proteins.
authors.affiliation: Laboratory of Toxicology and Applied Pharmacology, Catholic University of Louvain, Brussels, Belgium.
authors.forename: Agnes
authors.initials: A
authors.lastname: Chaumont
authors.forename: Catherine
authors.initials: C
authors.lastname: Voisin
authors.forename: Gladys
authors.initials: G
authors.lastname: Deumer
authors.forename: Vincent
authors.initials: V
authors.lastname: Haufroid
authors.forename: Isabella
authors.initials: I
authors.lastname: Annesi-Maesano
authors.forename: Harry
authors.initials: H
authors.lastname: Roels
authors.forename: Lutgarde
authors.initials: L
authors.lastname: Thijs
authors.forename: Jan
authors.initials: J
authors.lastname: Staessen
authors.forename: Alfred
authors.initials: A
authors.lastname: Bernard
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000652:urine*; D001530:Belgium; D002104:Cadmium / Q000652:urine*; D002648:Child; D003404:Creatinine / Q000652:urine; D005260:Female; D006023:Glycoproteins / Q000652:urine; D006801:Humans; D008297:Male; D008875:Middle Aged; D012177:Retinol-Binding Proteins / Q000652:urine*; D012709:Serum Albumin / Q000032:analysis; D000075462:Serum Albumin, Human; D012907:Smoking; D016482:Urinalysis / Q000379:methods
chemical_list: C422455:ALB protein, human; D006023:Glycoproteins; D012177:Retinol-Binding Proteins; D012709:Serum Albumin; D002104:Cadmium; D003404:Creatinine; D000075462:Serum Albumin, Human