Cystatin C is a protein that is produced by the cells in your body. When kidneys are working well, they keep the level of cystatin C in your blood just right. If the level of cystatin C in your blood is too high, it may mean that your kidneys are not working well.
A blood test for cystatin C can help your healthcare provider find your GFR (glomerular filtration rate). Your GFR number helps your healthcare provider know how well your kidneys are working.
Your GFR tells a lot about how well your kidneys are working. Your kidneys are important. They filter our waste and extra water from your body, help make red blood cells, and keep your bones strong. If your GFR number is low, your kidneys may not be working as well as they should. This may be a sign of kidney disase.
Another way to estimate GFR is with a simple blood test for cystatin C. Like creatinine, the cystatin C number is used in a math formula with your age, race, and gender to estimate your GFR. The cystatin C test is not the usual or regular way that your healthcare provider will estimate your GFR. But it can be very helpful in some instances.
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. However, testing is becoming increasingly more available and steps are being taken toward standardizing the calibration of cystatin C results.
A cystatin C blood test can be helpful if:
- A previous test for kidney function was inconclusive or needs to be confirmed. In this instance, your healthcare provider may give you cystatin C test to confirm whether or not you have kidney disease.
- You are overweight, elderly or have lots of muscle (such as a body builder). Cystatin C-based estimates for GFR are believed to be less influenced by muscle mass or diet than creatinine-based estimates.
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 blood.
The rate at which the fluid is filtered is called the glomerular filtration rate (GFR). A decline in kidney function leads to decreases in the GFR and to increases in cystatin C and other measures of kidney function, such as creatinine and urea in the blood. The increases in these levels occur because the kidneys are not able to properly filter the blood at a normal rate, causing their accumulation in the blood. On the other hand, improvement in kidney function is expected to lead to increases in GFR, which would cause cystatin C, creatinine, and urea to decline as a result of the kidneys being able to effectively clear them from the blood.
When the kidneys are functioning normally, concentrations of cystatin C in the blood are stable. However, as kidney function deteriorates, the concentrations begin to rise. This increase in cystatin C occurs as the GFR falls and is often detectable before there is a measurable decrease in kidney function (GFR).
Ebert N, Delanaye P, Shlipak M, Jakob O, Martus P, Bartel J, Gaedeke J, van der Giet M, Schuchardt M, Cavalier E, Schaeffner E. Cystatin C standardization decreases assay variation and improves assessment of glomerular filtration rate. Clin Chim Acta. 2016 May 1;456:115-21. 
Kidney Disease Improving Global Outcomes, KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. 
Inker LA, Schmid CH, Tighiouart H, Eckfeldt JH, Feldman HI, Greene T, Kusek JW, Manzi J, Van Lente F, Zhang YL, Coresh J, Levey AS.; CKD-EPI Investigators Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med. 2012 Jul 5;367(1):20-9. 
Waheed S, Matsushita K, Sang Y, Hoogeveen R, Ballantyne C, Coresh J, Astor BC. Combined association of albuminuria and cystatin C-based estimated GFR with mortality, coronary heart disease, and heart failure outcomes: the Atherosclerosis Risk in Communities (ARIC) Study. Am J Kidney Dis. 2012 Aug;60(2):207-16. 
Dalcomune DM, Terrão J, Porto ML, Vasquez EC, Baldo MP, Pereira TM. Predictive value of cystatin C for the identification of illness severity in adult patients in a mixed intensive care unit. Clin Biochem. 2016 Jul;49(10-11):762-7. 
Brown CS, Kashani KB, Clain JM, Frazee EN. Cystatin C Falsely Underestimated GFR in a Critically Ill Patient with a New Diagnosis of AIDS. Case Rep Nephrol. 2016;2016:9349280. 
A high level of cystatin C in the blood corresponds to a decreased glomerular filtration rate (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.
Recent studies suggest that increased levels of cystatin C may also indicate an increased risk of heart disease, heart failure, and mortality.
Although cystatin C is less variable and less affected by age, body mass, and diet than creatinine in some individuals, it is not a perfect test and can be affected by a number of drugs and other medical conditions.
Some studies have reported increased cystatin C levels associated with higher levels of C-reactive protein (CRP) or body mass index (BMI), hyperthyroidism, steroid use, malignant diseases, HIV/AIDS, rheumatic diseases, and certain metabolic conditions such as hyperhomocysteinemia (increased homocysteine). In addition, other studies suggest that cystatin C can be cleared by non-kidney pathways, such as in the gut, and that its levels tend to fluctuate among patients with kidney transplants.
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