To assess your kidney function if you have known or suspected kidney disease, but only in specific circumstances when traditional kidney function tests are misleading. It is used to calculate how well your kidneys are able to filter waste products from the blood.
When your doctor suspects that you may have decreased kidney function but blood creatinine measurements are not reliable because of circumstances specific to you. It may be measured at intervals over a longer time to monitor your kidney function.
A blood sample taken from a vein in your arm
In healthy people, blood concentrations of cystatin C remain relatively constant throughout life. If kidney function declines, the blood concentration rises.
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 kidneys reabsorb cystatin C, glucose and other substances from this fluid. The remaining fluid and wastes are carried to the bladder and excreted as urine. The reabsorbed cystatin C is broken down in the kidney cells and is not returned to the blood.
The rate at which the filtrate fluid is formed is called the Glomerular Filtration Rate (GFR), which is an important determinant of kidney function. A decline in kidney function leads to a decrease in the GFR, so less cystatin C is cleared from the blood and the concentration rises.
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, with some cancers or in people taking steroid medication.
Because cystatin C concentrations fluctuate with changes in GFR, the cystatin C test can be used to evaluate kidney function and estimate the GFR. More commonly used blood tests include creatinine, a by-product of muscle metabolism, 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 disorders. Creatinine is the most widely used but is affected by muscle mass, how much meat you eat, age, race and gender. Cystatin C is much less affected by these. 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, the concentration of cystatin C in the blood is stable, but as kidney function deteriorates, the concentration begins to rise, often before that of creatinine. This increase occurs as the GFR falls and is usually detectable before a person has any symptoms of kidney disease.
Creatinine and cystatin C can be used alone or in combination to calculate an estimated GFR. The calculations use race, age and gender as well as the concentrations measured by the blood test. This calculated estimate of GFR is a more accurate measure of kidney function than the blood concentrations of cystatin C or creatinine alone.
How is the sample collected for testing?
A blood sample is obtained by inserting a needle into a vein in your 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 to look for and monitor kidney dysfunction in people with known or suspected kidney diseases. It is most useful in situations where creatinine measurement could be misleading: for instance in those who have liver cirrhosis, are very muscular, obese, malnourished or have a very small muscle mass (elderly, children or people with amputated limbs).
It can be useful in the early detection of chronic kidney disease (CKD), when other test results may still be normal and an affected person has few, if any, symptoms. There is some research suggesting that cystatin C returns to normal much more quickly than creatinine and could be used to assess kidney function in critically ill patients recovering in hospital.
When is it requested?
Blood creatinine is the most commonly used test of kidney function. Cystatin C can be used if measurement of creatinine is likely to be misleading. It may be requested when you have a known or suspected disorder that affects kidney function, even if you have no symptoms. 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.
In the UK, the National Institute for Health and Care excellence (NICE) recommends testing people if their estimated GFR based on measurement of blood creatinine is borderline low and they have no other evidence of kidney disease. If the estimated GFR is normal using cystatin C, further monitoring for kidney disease is not usually required.
What does the test result mean?
A high blood concentration of cystatin C indicates a low GFR and hence decreased filtration of waste products from the blood by the kidneys. Research suggests that it may also indicate an increased risk of heart disease, heart failure, stroke, and mortality.
Since cystatin C is produced throughout the body at a constant rate and removed and broken down by the kidneys, it remains at a steady concentration in the blood if the kidneys are working efficiently and the GFR is normal.
Concentrations of cystatin C vary little with sex, age or race and are not affected by most drugs, infections or diet. However, they may be increased by steroid medication, smoking and inflammation.
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 test 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 kidney tubules. 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 the urine of healthy people.
How is an estimated GFR (eGFR) calculated?
The equation recommended by NICE for calculating the eGFR, is called the CKD-EPI equation. It uses a person’s serum creatinine, age, gender and race for the calculation.
The CKD-EPI equation has variants that use creatinine alone, cystatin C alone, or a combination of both values.
Elsewhere On The Web
ACB, Analyte Monographs (AMALC): Cystatin C
NICE guidelines – information for the public
NHS: Chronic kidney disease
National Kidney Foundation
The Renal Association