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Associations between Urinary Excretion of Cadmium and Proteins in a Nonsmoking Population: Renal Toxicity or Normal Physiology?

Akerstrom, Magnus; Sallsten, Gerd; Lundh, Thomas LU and Barregard, Lars (2013) In Environmental Health Perspectives 121(2). p.187-191
Abstract
BACKGROUND: Associations between cadmium (Cd) and kidney function have been reported even at low levels of exposure in the general population. Recently, the causality of these associations has been questioned. OBJECTIVES: We examined associations between urinary Cd (U-Cd; a biomarker of exposure) and urinary proteins that are used as biomarkers of kidney effects, based on repeated short-term sampling in healthy subjects. METHODS: Twenty-four hour urine samples were collected on 2 separate days at six fixed times from 30 healthy nonsmoking men and women (median age 39 years). We analyzed the samples (N = 354) for Cd (i.e., U-Cd) and two proteins used as kidney function biomarkers: urinary albumin (U-Alb) and alpha-1-microglobulin (U-A1M).... (More)
BACKGROUND: Associations between cadmium (Cd) and kidney function have been reported even at low levels of exposure in the general population. Recently, the causality of these associations has been questioned. OBJECTIVES: We examined associations between urinary Cd (U-Cd; a biomarker of exposure) and urinary proteins that are used as biomarkers of kidney effects, based on repeated short-term sampling in healthy subjects. METHODS: Twenty-four hour urine samples were collected on 2 separate days at six fixed times from 30 healthy nonsmoking men and women (median age 39 years). We analyzed the samples (N = 354) for Cd (i.e., U-Cd) and two proteins used as kidney function biomarkers: urinary albumin (U-Alb) and alpha-1-microglobulin (U-A1M). Concentrations were adjusted for creatinine concentration or for specific gravity, and excretion rates (mass per hour) were calculated. Possible associations were assessed within each individual participant, and mean correlations and regressions were evaluated. RESULTS: We found clear positive mean associations within individuals between the excretion of U-Cd [mean, 0.11 mu g/g creatinine (range, 0.01-0.52 mu g/g creatinine)] and both U-Alb and U-A1M. The associations were stronger for excretion rates and concentrations adjusted for specific gravity than for concentrations adjusted for creatinine. We also found significant positive associations of urinary flow with excretion of U-Cd, U-Alb, and U-A1M. CONCLUSIONS: Associations between short-term changes in U-Cd and markers of kidney function within individual nonsmoking study participants are unlikely to reflect effects of Cd toxicity. A more likely explanation is that these associations result from normal variation in renal function, including changes in urinary flow, that influence the urinary excretion of both Cd and proteins in the same direction. These effects of normal variability may result in overestimation of the adverse effects of Cd on kidney function at low-level Cd exposure. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
albumin, alpha-1-microglobulin, cadmium, cadmium toxicity, kidney, effect, renal function, urinary excretion
in
Environmental Health Perspectives
volume
121
issue
2
pages
187 - 191
publisher
National Institute of Environmental Health Science
external identifiers
  • wos:000323700900019
  • scopus:84873363059
ISSN
1552-9924
DOI
10.1289/ehp.1205418
language
English
LU publication?
yes
id
878947ab-65f9-4614-8b80-68997ce55417 (old id 4063628)
date added to LUP
2014-03-03 08:12:48
date last changed
2019-10-15 04:21:51
@article{878947ab-65f9-4614-8b80-68997ce55417,
  abstract     = {BACKGROUND: Associations between cadmium (Cd) and kidney function have been reported even at low levels of exposure in the general population. Recently, the causality of these associations has been questioned. OBJECTIVES: We examined associations between urinary Cd (U-Cd; a biomarker of exposure) and urinary proteins that are used as biomarkers of kidney effects, based on repeated short-term sampling in healthy subjects. METHODS: Twenty-four hour urine samples were collected on 2 separate days at six fixed times from 30 healthy nonsmoking men and women (median age 39 years). We analyzed the samples (N = 354) for Cd (i.e., U-Cd) and two proteins used as kidney function biomarkers: urinary albumin (U-Alb) and alpha-1-microglobulin (U-A1M). Concentrations were adjusted for creatinine concentration or for specific gravity, and excretion rates (mass per hour) were calculated. Possible associations were assessed within each individual participant, and mean correlations and regressions were evaluated. RESULTS: We found clear positive mean associations within individuals between the excretion of U-Cd [mean, 0.11 mu g/g creatinine (range, 0.01-0.52 mu g/g creatinine)] and both U-Alb and U-A1M. The associations were stronger for excretion rates and concentrations adjusted for specific gravity than for concentrations adjusted for creatinine. We also found significant positive associations of urinary flow with excretion of U-Cd, U-Alb, and U-A1M. CONCLUSIONS: Associations between short-term changes in U-Cd and markers of kidney function within individual nonsmoking study participants are unlikely to reflect effects of Cd toxicity. A more likely explanation is that these associations result from normal variation in renal function, including changes in urinary flow, that influence the urinary excretion of both Cd and proteins in the same direction. These effects of normal variability may result in overestimation of the adverse effects of Cd on kidney function at low-level Cd exposure.},
  author       = {Akerstrom, Magnus and Sallsten, Gerd and Lundh, Thomas and Barregard, Lars},
  issn         = {1552-9924},
  keyword      = {albumin,alpha-1-microglobulin,cadmium,cadmium toxicity,kidney,effect,renal function,urinary excretion},
  language     = {eng},
  number       = {2},
  pages        = {187--191},
  publisher    = {National Institute of Environmental Health Science},
  series       = {Environmental Health Perspectives},
  title        = {Associations between Urinary Excretion of Cadmium and Proteins in a Nonsmoking Population: Renal Toxicity or Normal Physiology?},
  url          = {http://dx.doi.org/10.1289/ehp.1205418},
  volume       = {121},
  year         = {2013},
}