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Associations between proteins and heavy metals in urine at low environmental exposures: Evidence of reverse causality

Chaumont, Agnes; Nickmilder, Marc; Dumont, Xavier; Lundh, Thomas LU ; Skerfving, Staffan LU and Bernard, Alfred (2012) In Toxicology Letters 210(3). p.345-352
Abstract
Heavy metals can cause renal effects on vulnerable populations but it is uncertain whether these metals still pose health risks at the low exposure levels now prevailing in most industrialized countries. In a cross-sectional study performed on 736 adolescents, we assessed the associations between the concentrations of cadmium and lead in blood and urine and the urinary concentrations of albumin and of low-molecular-weight (LMW) proteins, retinol-binding protein (RBP) and beta(2)-microglobulin. Multiple regression analyses were tested using urinary markers normalized to urinary creatinine or specific gravity. Median metal concentrations were in blood (mu g/L): lead. 15.1, cadmium, 0.18 and in urine (mu g/g creatinine): cadmium, 0.09 and... (More)
Heavy metals can cause renal effects on vulnerable populations but it is uncertain whether these metals still pose health risks at the low exposure levels now prevailing in most industrialized countries. In a cross-sectional study performed on 736 adolescents, we assessed the associations between the concentrations of cadmium and lead in blood and urine and the urinary concentrations of albumin and of low-molecular-weight (LMW) proteins, retinol-binding protein (RBP) and beta(2)-microglobulin. Multiple regression analyses were tested using urinary markers normalized to urinary creatinine or specific gravity. Median metal concentrations were in blood (mu g/L): lead. 15.1, cadmium, 0.18 and in urine (mu g/g creatinine): cadmium, 0.09 and lead, 0.82. Multivariate analyses revealed significant associations in urine between RBP and cadmium as well as between beta(2)-microglobulin and lead whereas no associations were seen with metals in blood. These associations were completely abolished in subjects with increased urinary albumin, which may be explained by the competitive inhibition of LMW protein reabsorption by albumin. Given the evidence that cadmium and lead circulate mainly bound to LMW proteins, these associations observed at low exposure might simply reflect the interindividual variations in the renal uptake of proteins sharing the same affinity for tubular binding sites. (C) 2012 Elsevier Ireland Ltd. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cadmium, Lead, Heavy metals, Proteinuria, Albuminuria, Retinol-binding, protein, beta(2)-microglobulin, Reverse causality
in
Toxicology Letters
volume
210
issue
3
pages
345 - 352
publisher
Elsevier
external identifiers
  • wos:000303623600011
  • scopus:84858964143
ISSN
1879-3169
DOI
10.1016/j.toxlet.2012.02.005
language
English
LU publication?
yes
id
fef1d631-db9a-4a98-9b4b-d3e2e39cf3ee (old id 2545456)
date added to LUP
2012-06-01 08:56:24
date last changed
2017-11-19 03:45:27
@article{fef1d631-db9a-4a98-9b4b-d3e2e39cf3ee,
  abstract     = {Heavy metals can cause renal effects on vulnerable populations but it is uncertain whether these metals still pose health risks at the low exposure levels now prevailing in most industrialized countries. In a cross-sectional study performed on 736 adolescents, we assessed the associations between the concentrations of cadmium and lead in blood and urine and the urinary concentrations of albumin and of low-molecular-weight (LMW) proteins, retinol-binding protein (RBP) and beta(2)-microglobulin. Multiple regression analyses were tested using urinary markers normalized to urinary creatinine or specific gravity. Median metal concentrations were in blood (mu g/L): lead. 15.1, cadmium, 0.18 and in urine (mu g/g creatinine): cadmium, 0.09 and lead, 0.82. Multivariate analyses revealed significant associations in urine between RBP and cadmium as well as between beta(2)-microglobulin and lead whereas no associations were seen with metals in blood. These associations were completely abolished in subjects with increased urinary albumin, which may be explained by the competitive inhibition of LMW protein reabsorption by albumin. Given the evidence that cadmium and lead circulate mainly bound to LMW proteins, these associations observed at low exposure might simply reflect the interindividual variations in the renal uptake of proteins sharing the same affinity for tubular binding sites. (C) 2012 Elsevier Ireland Ltd. All rights reserved.},
  author       = {Chaumont, Agnes and Nickmilder, Marc and Dumont, Xavier and Lundh, Thomas and Skerfving, Staffan and Bernard, Alfred},
  issn         = {1879-3169},
  keyword      = {Cadmium,Lead,Heavy metals,Proteinuria,Albuminuria,Retinol-binding,protein,beta(2)-microglobulin,Reverse causality},
  language     = {eng},
  number       = {3},
  pages        = {345--352},
  publisher    = {Elsevier},
  series       = {Toxicology Letters},
  title        = {Associations between proteins and heavy metals in urine at low environmental exposures: Evidence of reverse causality},
  url          = {http://dx.doi.org/10.1016/j.toxlet.2012.02.005},
  volume       = {210},
  year         = {2012},
}