Biomarker Information

Cystatin C

Biomarker of Kidney Function

Cystatin C is found in virtually all tissues and is an extracellular cysteine protease inhibitor that belongs to the cystatin superfamily. It is a potent inhibitor of lysosomal proteinases and probably one of the most important extracellular inhibitors of cysteine proteases.

Serum Cystatin C has mainly been used as a biomarker of kidney function, but recently its utility has been broadening to cardiovascular disease. Because of its small size and basic pH, Cystatin C is freely filtered by the glomerulus. It is then reabsorbed by tubular epithelial cells and subsequently metabolized. Urine Cystatin C measurement is also specific for tubular kidney damage.

Beside kidney function Cystatin C has recently also been suggested as being involved in predicting new-onset or deteriorating cardiovascular disease. Several studies have found that increased levels of Cystatin C are associated with the risk of death and several types of cardiovascular disease, such as myocardial infarction, stroke, heart failure, and peripheral arterial disease.

References

1. Zethelius B, Berglund L, Sundström J, et al. (May 2008). “Use of multiple biomarkers to improve the prediction of death from cardiovascular causes”. N. Engl. J. Med. 358(20): 2107–16. doi:10.1056/NEJMoa0707064PMID18480203.
2. Shlipak MG, Sarnak MJ, Katz R, et al. (May 2005). “Cystatin C and the risk of death and cardiovascular events among elderly persons”. N. Engl. J. Med. 352 (20): 2049–60. doi:10.1056/NEJMoa043161PMID 15901858.
3. Ix JH, Shlipak MG, Chertow GM, Whooley MA (January 2007). “Association of cystatin C with mortality, cardiovascular events, and incident heart failure among persons with coronary heart disease: data from the Heart and Soul Study”. Circulation 115 (2): 173–9. doi:10.1161/CIRCULATIONAHA.106.644286PMID17190862.PMC 2771187.
4. Deo R, Fyr CL, Fried LF, et al. (January 2008). “Kidney dysfunction and fatal cardiovascular disease–an association independent of atherosclerotic events: results from the Health, Aging, and Body Composition (Health ABC) study”. Am. Heart J. 155 (1): 62–8. doi:10.1016/j.ahj.2007.08.012PMID 18082491.
5. Koenig W, Twardella D, Brenner H, Rothenbacher D (February 2005). “Plasma concentrations of cystatin C in patients with coronary heart disease and risk for secondary cardiovascular events: more than simply a marker of glomerular filtration rate”. Clin. Chem. 51 (2): 321–7. doi:10.1373/clinchem.2004.041889PMID 15563478.
6. Jernberg T, Lindahl B, James S, Larsson A, Hansson LO, Wallentin L (October 2004). “Cystatin C: a novel predictor of outcome in suspected or confirmed non-ST-elevation acute coronary syndrome”. Circulation 110 (16): 2342–8. doi:10.1161/01.CIR.0000145166.44942.E0PMID 15477399.
7. Luc G, Bard JM, Lesueur C, et al. (April 2006). “Plasma cystatin-C and development of coronary heart disease: The PRIME Study”. Atherosclerosis 185 (2): 375–380. doi:10.1016/ j.atherosclerosis.2005.06.017. PMID 16046222.
8. Dieterle F, Perentes E, Cordier A, et al. (May 2010). ” Urinary clusterin, cystatin C, β2-microglobulin and total protein as markers to detect drug-induced kidney injury”. Nature Biotechnology 28(5): 463 – 472

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