Cystatin C
At a Glance
Why Get Tested?
To help detect and monitor acute and chronic kidney dysfunction; its ultimate clinical utility has yet to be fully established
When to Get Tested?
When a doctor suspects that a person may have decreased kidney function, especially when a patient has normal creatinine and eGFR test results; may be ordered at intervals when a person has known kidney dysfunction
Sample Required?
A blood sample drawn from a vein in your arm
Test Preparation Needed?
None
The Test Sample
What is being tested?
Cystatin C is a relatively small protein that is produced throughout the body by nucleated (containing a nucleus) cells. It is produced and destroyed at a constant rate and is found in a variety of body fluids, such as blood, spinal fluid, and breast milk.
Cystatin C is filtered out of the blood by the glomeruli, clusters of tiny blood vessels in the kidneys that allow water, dissolved substances, and wastes to pass through their walls while retaining blood cells and larger proteins. What passes through the walls of the glomeruli forms a filtrate fluid. From this fluid, the kidneys reabsorb Cystatin C, glucose, and other substances. The remaining fluid and wastes are carried to the bladder and excreted as urine. The reabsorbed Cystatin C is then broken down and is not returned to the bloodstream.
The rate at which the fluid is filtered is called the glomerular filtration rate (GFR). Decreases in kidney function lead to decreases in the GFR and to increases in Cystatin C and waste products in the blood.
Because Cystatin C levels fluctuate with changes in GFR, there has been interest in the Cystatin C test as one method of evaluating kidney function. Tests currently used include creatinine, a byproduct of muscle metabolism that is measured in the blood and urine, BUN (Blood Urea Nitrogen), and eGFR – an estimate of the GFR. Unlike creatinine, Cystatin C is not significantly affected by muscle mass, gender, age, or race. When the kidneys are functioning normally, concentrations of Cystatin C in the blood are stable, but as kidney function deteriorates, the concentrations begin to rise. This increase occurs as the GFR falls and is often detectable before there is a measurable decrease in the GFR. While there are growing data and literature supporting the use of Cystatin C, there is still a degree of uncertainty about when and how it should be used.
How is the sample collected for testing?
A blood sample is obtained by inserting a needle into a vein in the arm.
NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.
Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.
Is any test preparation needed to ensure the quality of the sample?
No test preparation is needed.
The Test
How is it used?
Cystatin C may be used as an alternative to creatinine and creatinine clearance to screen for and monitor kidney dysfunction in those with known or suspected kidney diseases. It may be especially useful in those cases where creatinine measurement is not appropriate, for instance, in those who have liver cirrhosis, are very obese, are malnourished or have a reduced muscle mass. Measuring Cystatin C may also be useful in the early detection of kidney disease when other test results may still be normal and an affected person may have few, if any, symptoms.
Researchers are exploring other uses of Cystatin C, and the reasons for doctors ordering it may evolve over time. In addition to kidney dysfunction, it has been associated with an increased risk of cardiovascular disease and heart failure in older adults.
When is it ordered?
Cystatin C is gaining acceptance as studies confirm and define its usefulness, especially as an early, sensitive marker for chronic kidney disease. It may be ordered when a person has a known or suspected disease that affects or potentially affects kidney function and reduces the glomerular filtration rate (GFR). It may be ordered when a doctor is not satisfied with the results of other tests, such as a creatinine, estimated GFR, or creatinine clearance, or when he wants to check for early kidney dysfunction, particularly in the elderly, and/or wants to monitor known impairment over time.
Researchers are hoping to learn more about Cystatin C as an indicator of risk of heart failure and death, especially in older patients. In this case, the test may prove useful at times when a patient is at an increased risk of heart problems. For example, the test may be ordered as part of preoperative screening, before prescribing certain medications, or before performing scans that use intravenous dyes.
What does the test result mean?
An increased serum Cystatin C corresponds to a decreased GFR and hence to kidney dysfunction. Since Cystatin C is produced throughout the body at a constant rate and removed and broken down by the kidneys, it should remain at a steady level in the blood if the kidneys are working efficiently and the GFR is normal. Concentrations of Cystatin C are not affected by gender, age, or race and Cystatin C is not affected by most drugs (see below), infections, diet, or inflammation.
Recent studies suggest that increased levels of Cystatin C may also indicate an increased risk of heart disease, heart failure, stroke, and mortality.
Is there anything else I should know?
Cystatin C has been associated with hyperhomocysteinemia, which is often found in renal transplant patients, and it has been shown to increase with the progression of liver disease. At least one study has looked at comparing Cystatin C levels in serum with that found in pleural effusion to help determine the cause of the effusion. These associations may or may not prove clinically useful.
Corticosteroids can increase levels Cystatin C levels while cyclosporine can decrease them. In the absence of kidney disease, Cystatin C levels may be elevated in rheumatic diseases and in malignant diseases, although they are not affected by tumor burden, the amount of cancer that someone has.
Common Questions
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Article Sources
NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.
Sources Used in Current Review
Wu, A. (© 2006). Tietz Clinical Guide to Laboratory Tests, 4th Edition: Saunders Elsevier, St. Louis, MO. Pp 328-329.
Clarke, W. and Dufour, D. R., Editors (© 2006). Contemporary Practice in Clinical Chemistry: AACC Press, Washington, DC. Pp 312.
Lowry, F. (2009 February 27). Cystatin C, High Levels of Serum Cystatin C and Chronic Kidney Disease Linked to Age-Related Macular Degeneration. Medscape Medical News [On-line information]. Available online at http://www.medscape.com/viewarticle/588857 through http://www.medscape.com. Accessed October 2009.
Ma, Y-C. et. al. (2008 January 28). Improved GFR Estimation by Combined Creatinine and Cystatin C Measurements. Medscape Today from Kidney International [On-line information]. Available online at http://www.medscape.com/viewarticle/568609 through http://www.medscape.com. Accessed October 2009.
Craig, R. G. and Hunder, J. M. (2008 October 27). Recent Developments in the Perioperative Management of Adult Patients with Chronic Kidney Disease. Medscape Today from British Journal of Anaesthesia [On-line information]. Available online at http://www.medscape.com/viewarticle/581312 through http://www.medscape.com. Accessed October 2009.
(2009 January 27). New Equation Accurately Estimates GFR in Children With Kidney Disease. Medscape Today from Reuters Health Information [On-line information]. Available online at http://www.medscape.com/viewarticle/587379 through http://www.medscape.com. Accessed October 2009.
(Updated 2009 August). Renal Function Markers - Kidney Disease. ARUP Consult. [On-line information]. Available online at http://www.arupconsult.com/Topics/RenalFunctionMarkers.html?client_ID=LTD through http://www.arupconsult.com. Accessed October 2009.
(April 7, 2009) National Kidney Disease Education Program, Laboratory Professionals: Update on Cystatin C. Available online at http://nkdep.nih.gov/labprofessionals/update-cystatin-c.htm through http://nkdep.nih.gov. Accessed January 2010.
Henry's Clinical Diagnosis and Management by Laboratory Methods. 21st ed. McPherson R, Pincus M, eds. Philadelphia, PA: Saunders Elsevier: 2007, Pp 153-154.
Sources Used in Previous Reviews
Thomas, Clayton L., Editor (1997). Taber's Cyclopedic Medical Dictionary. F.A. Davis Company, Philadelphia, PA [18th Edition].
Jeffrey, S. (2006 August 16). Cystatin C May Identify Pre-CKD in Elderly With Normal eGFR. Medscape Medical News [On-line information]. Available online at http://www.medscape.com/viewarticle/543019 through http://www.medscape.com.
Jeffrey, S. (2005 September 6). Cystatin C is a sensitive marker of prognosis acute heart failure. Medscape Medical News [On-line information]. Available online at http://www.medscape.com/viewarticle/538789 through http://www.medscape.com.
Shlipak, M. (2005 May 19). Cystatin C and the Risk of Death and Cardiovascular Events among Elderly Persons. NEJM v 352(20) 2049-2060 [On-line journal]. Available online at http://content.nejm.org/cgi/content/short/352/20/2049 through http://content.nejm.org.
Sarnak, M. (2005 April 5). Cystatin C Concentration as a Risk Factor for Heart Failure in Older Adults. Annals of Internal Medicine v142(7) [On-line information]. Available online at http://www.annals.org/cgi/content/abstract/142/7/497?ct through http://www.annals.org.
Villa, P. et. al. (2005 April). Serum cystatin C concentration as a marker of acute renal dysfunction in critically ill patients. Crit Care. 2005; 9(2): R139-R143 [On-line journal]. Available online at http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=1175926 through http://www.pubmedcentral.gov.
