title: Low serum zinc is associated with elevated risk of cadmium nephrotoxicity.
abstract: BACKGROUND
  Despite animal evidence suggests that zinc modulates cadmium nephrotoxicity, limited human data are available.
  
  
  OBJECTIVE
  To test the hypothesis that low serum zinc concentrations may increase the risk of cadmium-mediated renal dysfunction in humans.
  
  
  METHODS
  Data from 1545 subjects aged 20 or older in the National Health and Nutrition Examination Survey (NHANES), 2011-2012 were analyzed. Renal function was defined as impaired when estimated glomerular filtration rate (eGFR) fell below 60 ml/min/1.73 m(2) and/or the urinary albumin-to-creatinine ratio surpassed 2.5 in men and 3.5mg/mmol in women.
  
  
  RESULTS
  Within the study cohort, 117 subjects had reduced eGFR and 214 had elevated urinary albumin. After adjusting for potential confounders, subjects with elevated blood cadmium (>0.53 μg/L) were more likely to have a reduced eGFR (odds ratio [OR]=2.21, 95% confidence interval [CI]: 1.09-4.50) and a higher urinary albumin (OR=2.04, 95% CI: 1.13-3.69) than their low cadmium (<0.18 μg/L) peers. In addition, for any given cadmium exposure, low serum zinc is associated with elevated risk of reduced eGFR (OR=3.38, 95% CI: 1.39-8.28). A similar increase in the odds ratio was observed between declining serum zinc and albuminuria but failed to reach statistical significance. Those with lower serum zinc/blood cadmium ratios were likewise at a greater risk of renal dysfunction (p<0.01).
  
  
  CONCLUSIONS
  This study results suggest that low serum zinc concentrations are associated with an increased risk of cadmium nephrotoxicity. Elevated cadmium exposure is global public health issue and the assessment of zinc nutritional status may be an important covariate in determining its effective renal toxicity.
authors.affiliation: National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC, USA. Electronic address: Lin.Yu-Sheng@epa.gov.
authors.forename: Yu-Sheng
authors.initials: YS
authors.lastname: Lin
authors.affiliation: Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan.
authors.forename: Wen-Chao
authors.initials: WC
authors.lastname: Ho
authors.affiliation: Integrative Physiology and Cardiovascular Research Institute, University of North Texas Health Science Center, Fort Worth, TX, USA.
authors.forename: James L
authors.initials: JL
authors.lastname: Caffrey
authors.affiliation: National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC, USA.
authors.forename: Babasaheb
authors.initials: B
authors.lastname: Sonawane
mesh_terms: D000328:Adult; D000368:Aged; D002104:Cadmium / Q000633:toxicity*; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D055815:Young Adult; D015032:Zinc / Q000097:blood*
chemical_list: D002104:Cadmium; D015032:Zinc
keywords: Albuminuria; Cadmium; Glomerular filtration rate; Kidney; Renal; Zinc