Cystatin C measurement is becoming more widely available in the UK to assess kidney function. It is particularly helpful in situations where measurements of creatinine (the commonest way of assessing kidney function) are misleading or difficult to interpret. It is used to monitor people with known or suspected kidney diseases. It is used to calculate how well your kidneys are able to filter waste products from the blood.
It can be useful if you have symptoms of kidney disease and/or have a disease or condition that is known to affect kidney function
A blood sample taken from a vein in your arm
Cystatin C is a small protein that is produced by all cells that contain a nucleus (i.e. the majority of cells in the body). In healthy people, 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 which are clusters of tiny blood vessels in the kidneys that allow water and 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. The rate at which this fluid is formed is called the Glomerular Filtration Rate (GFR), which is an important determinant of kidney function. The proximal tubules of 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 broken down in the tubular cells and is not returned to the bloodstream. Decreases in kidney function lead to decreases in the GFR, and to increases in cystatin C and waste products in the blood. Rarely, high blood concentrations of cystatin C are the result of increased production by cells rather than a kidney problem, for example in people with an overactive thyroid or with some cancers.
Because cystatin C concentrations fluctuate with changes in GFR, the cystatin C test can be used to evaluate kidney function and estimate the GFR. Tests more commonly used include creatinine, a by-product of muscle metabolism that is measured in the blood and urine, and urea, a by-product of protein breakdown. Urea is the least reliable of these tests as it is affected by diet and many other diseases, not just kidney dysfunction. Unlike creatinine, cystatin C concentration is not significantly affected by muscle mass or the amount of meat eaten in the preceding 12 hours and is less affected by age, race and gender. In people with very high or low muscle bulk, estimates of GFR based on measurements of creatinine concentration will not be reliable, in contrast to those based on cystatin C.
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, often before those of creatinine. This increase occurs as the GFR falls and is usually detectable before there are any symptoms of kidney disease.
Creatinine and cystatin C can be used alone or in combination to calculate an estimated GFR. The calculations include factors such as age and gender as well as the measured concentrations of the substances. The estimated GFR is a more accurate measure of kidney function than the blood concentrations of cystatin C or creatinine alone.
In the UK, the National Institute for Health and Care excellence (NICE) recommends testing patients in whom an estimated GFR based on measurement of blood creatinine is borderline low and there is no other evidence of kidney disease. If the estimated GFR is normal using a cystatin C based equation, further monitoring for kidney disease is not required.
How is the sample collected for testing?
A blood sample is obtained by inserting a needle into a vein in the arm.
Is any test preparation needed to ensure the quality of the sample?
No test preparation is needed.
How is it used?
Cystatin C may be used as an alternative to creatinine and creatinine clearance to look for and monitor kidney dysfunction in people with known or suspected kidney diseases. It may be especially useful in situations where creatinine measurement is not appropriate: for instance in those who have liver cirrhosis, are very obese, malnourished or have a very small muscle mass (creatinine is produced in the muscles). It 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 requesting it may change 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 requested?
When available, cystatin C may be requested when you have a known or suspected disease that affects or potentially affects kidney function and reduces the glomerular filtration rate (GFR). It may also be requested if your kidney function is found to be borderline using the more readily available creatinine test. Your doctor may request cystatin C to check for early kidney disease and/or to monitor known impairment over time. It may be requested by itself or be done along with other tests such as urine microalbumin.
Early kidney impairment may not cause elevated creatinine levels or symptoms. If your doctor is not satisfied with your creatinine GFR test or feels that your GFR would be better estimated by another test, cystatin C may prove to be a useful alternative.
What does the test result mean?
An elevated serum cystatin C indicates a low GFR and hence decreased filtration of waste products from the blood by the kidneys. 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 concentration in the blood if the kidneys are working efficiently and the GFR is normal.
Concentrations of cystatin C are not affected much by gender, age or race and cystatin C is not affected by most drugs, infections, diet or inflammation. Recent studies suggest that increased concentrations of cystatin C may also indicate an increased risk of of heart disease, heart failure, stroke, and mortality.
Rarely, cystatin C concentrations may be high because of increased production by cancer cells or an overactive thyroid gland, even if kidney function is normal.
Is there anything else I should know?
Cystatin C measurement has not been widely available in the past. However, it is now recommended by NICE for use when the more commonly available tests are not reliable enough, so is likely to become more frequently used in the future.
Cystatin C results are usually reported both as the measured concentration in the blood and as a calculated estimate of kidney function (GFR).
Can cystatin C be measured in my urine?
Yes. Very rarely, and usually in research settings, cystatin C may be measured in urine to assess the function of the proximal tubular cells of the kidneys. If these are not able to reabsorb the proteins and other substances that are normally filtered by the glomeruli, cystatin C passes into the urine. This is known as tubular proteinuria. Cystatin C is not found in detectable levels in the urine of healthy people.
Can cystatin C be used for anything besides a measure of GFR?
Researchers are exploring other uses of cystatin C and the reasons for doctors requesting it may change over time. So far, in addition to detecting kidney dysfunction, it appears to predict the development of cardiovascular (heart and blood vessel) problems and 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 (fluid that builds up in the lungs in a variety of conditions) to help determine the cause of the effusion. These associations may or may not prove clinically useful.
How is an estimated GFR (eGFR) calculated?
The equation recommended by NICE for calculating the eGFR, is CKD-EPI (Chronic Kidney Disease, Epidemiology Collaboration). It replaces the previously recommended MDRD (Modification of Diet in Renal Disease study) equation. Both require a person’s serum creatinine,age, and assigned values based upon gender and race.
The CKD-EPI equation has variants that use creatinine alone, cystatin C alone, or a combination of both values.
Elsewhere On The Web
The Renal Association
NICE guidelines – information for the public
NHS choices website information on chronic kidney disease
National Kidney Foundation (US charity) information on cystatin C
The Renal Association patient guide to eGFR