Prozialeck, Walter C.VanDreel, AaronAckerman, Christopher D.Stock, IanPapaeliou, AlexanderYasmine, ChristianWilson, KristenLamar, Peter C.Sears, Victoria L.Gasiorowski, Joshua Z.DiNovo, Karyn M.Vaidya, VishalEdwards, Joshua R.2016-03-012015Prozialeck, W. C., A. VanDreel, C. D. Ackerman, I. Stock, A. Papaeliou, C. Yasmine, K. Wilson, et al. 2015. “Evaluation of cystatin C as an early biomarker of cadmium nephrotoxicity in the rat.” Biometals 29 (1): 131-146. doi:10.1007/s10534-015-9903-3. http://dx.doi.org/10.1007/s10534-015-9903-3.0966-0844http://nrs.harvard.edu/urn-3:HUL.InstRepos:25658544Cadmium (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.en-USCadmiumBiomarkersCystatin CNephrotoxicityProximal tubuleJournal Article2016-03-0110.1007/s10534-015-9903-3