Evaluation of cystatin C as an early biomarker of cadmium nephrotoxicity in the rat

Walter C. Prozialeck, Aaron VanDreel, Christopher D. Ackerman, Ian Stock, Alexander Papaeliou, Christian Yasmine, Kristen Wilson, Peter C. Lamar, Victoria L. Sears, Joshua Z. Gasiorowski, Karyn M. Dinovo, Vishal S. Vaidya, Joshua R. Edwards

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Cadmium (Cd) is a nephrotoxic environmental pollutant that causes insidious injury to the proximal tubule that results in severe polyuria and proteinuria. Cystatin C is a low molecular weight protein that is being evaluated as a serum and urinary biomarker for various types of ischemic and nephrotoxic renal injury. The objective of the present study was to determine if cystatin C might be a useful early biomarker of Cd nephrotoxicity. Male Sprague-Dawley rats were given daily injections of Cd for up to 12 weeks. At 3, 6, 9 and 12 weeks, urine samples were analyzed for cystatin C, protein, creatinine, β2 microglobulin and kidney injury molecule-1. The results showed that Cd caused a significant increase in the urinary excretion of cystatin C that occurred 3-4 weeks before the onset of polyuria and proteinuria. Serum levels of cystatin C were not altered by Cd. Immunolabeling studies showed that Cd caused the relocalization of cystatin C from the cytoplasm to the apical surface of the epithelial cells of the proximal tubule. The Cd-induced changes in cystatin C labelling paralleled those of the brush border transport protein, megalin, which has been implicated as a mediator of cystatin C uptake in the proximal tubule. These results indicate that Cd increases the urinary excretion of cystatin C, and they suggest that this effect may involve disruption of megalin-mediated uptake of cystatin C by epithelial cells of the proximal tubule.

Original languageEnglish (US)
Pages (from-to)131-146
Number of pages16
Issue number1
StatePublished - Feb 1 2016
Externally publishedYes


  • Biomarkers
  • Cadmium
  • Cystatin C
  • Nephrotoxicity
  • Proximal tubule

ASJC Scopus subject areas

  • Biomaterials
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Metals and Alloys


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