Cystatin C is important for monitoring kidney function, but is there more to this marker? Read on to uncover how cystatin C can impact your health.

What is Cystatin C?

Cystatin C is a small protein made by most cells in your body. It inhibits the breakdown of proteins [1+, 2+].

The kidneys filter, break down, and remove cystatin C. In healthy people, cystatin C is produced and broken down at a constant rate. But if your kidneys are not working well, cystatin C builds up [3, 4, 5].

Cystatin C is more than just a marker of kidney health. It plays many roles. In turn, high levels can point to problems other than kidney disease [6].

Cystatin C Test

Your health care provider may need to know if your kidneys have suffered some form of damage or if they’re perfectly healthy. He or she can order a blood test to check your cystatin C levels. You don’t need to do to prepare for the test. All it takes is a blood sample, which will be drawn from a vein in your arm [7].

Normal Range

The normal range of cystatin C is [7]:

  • 0.53-0.92 mg/L (milligrams per liter) for adults under 50 years old
  • 0.58-1.02 mg/L for adults over 50 years old

Higher cystatin C levels can point to poor kidney function [4].

Cystatin C levels were slightly lower in adult women than in men in a study of 309 people. The difference was too small to warrant a different normal range based on gender [7].

The following ranges are normal in babies and children [8]:

  • Newborns (preterm): 1.34 – 2.57 mg/L
  • Newborns (full-term): 1.36 – 2.23 mg/L
  • 8 days to 1 year: 0.75 – 1.87 mg/L
  • 1- to 3-year-olds: 0.68 – 1.60 mg/L
  • 3- to 16-year-olds: 0.51 – 1.31 mg/L

Advantages and Disadvantages over Creatinine

Pros

Although creatinine blood levels are the “gold standard” for monitoring kidney disease, they can be unreliable [9].

As a waste product of muscle metabolism, creatinine levels can vary depending on a person’s muscle mass. For example, levels can be different in men and women, in the elderly and younger people. Even the amount of protein in the diet affects creatinine blood levels. Altogether, this makes calculating GFR from creatinine more difficult [5].

Cystatin C’s biggest advantage is its ability to detect mild kidney dysfunction – creatinine’s “blind area.” That’s because creatinine does not rise until 50% of the kidney stops working [10].

Cystatin C also rises faster than creatinine after acute kidney injury, such as from routine medical procedures (with radiocontrast agents). Fast detection of sudden kidney injury is important, as it allows for faster treatment and leads to better outcomes [4, 3, 11].

In a study of over 3k intensive care unit (ICU) survivors, those with higher cystatin C levels were more likely to die than those with high creatinine. As such, cystatin C may be a better measure of kidney function after critical illness. It can identify higher and lower risk patients [12].

Cons

On the downside, cystatin C is not a specific marker. It can increase due to various kidney-unrelated factors, such as aging, hyperthyroidism, and the use of corticosteroid drugs.

Additionally, cystatin C tests are more expensive than creatinine tests, although greater clinical use is making them more affordable nowadays [13].

Other Tests Your Doctor May Order

Most people with chronic kidney disease can be diagnosed with two tests: a urine test to check for protein and a blood test (serum creatinine and or cystatin C) to estimate GFR [14].

Cystatin C is often used with creatinine to estimate GFR (See “What is GFR?” below for more information). This may be to confirm suspected kidney damage, even if the creatinine levels do not yet show it. Using both is more also accurate than either one alone [15].

Blood urea nitrogen (BUN), a naturally occurring substance, is also used to measure how well the kidneys are working [16].

What is GFR (glomerular filtration rate)?

To better understand why doctors measure cystatin C in the blood, we need to take a deeper dive into the anatomy and physiology of the kidneys.

Basic Kidney Anatomy

Each kidney is made up of many small structures called nephrons. Each nephron contains a glomerulus: a tiny filter where salts, fluid, and waste leave the blood and head for the urine. The efficiency of the glomeruli is measured as the glomerular filtration rate, or GFR [17+].

Relation to Kidney Health

The kidneys need to be strong and healthy – with a high GFR – to filter the blood efficiently. GFR is the best indicator of how well your kidneys are working. But it has to be measured indirectly or estimated, pointing to how much blood passes through the kidneys in one minute [17+].

Since we can’t get in the kidneys and measure the blood flowing through each glomerulus, we have to turn to other ways of assessing their function.

The ideal way is to measure a chemical the kidneys regularly filter (e.g. inulin). This is a complex process and requires a hospital stay. As such, it is not routinely done.

The most common way to measure GFR is to estimate it. Formulas use information about your lab markers, including cystatin C. Higher cystatin C levels will give lower GFR (See “GFR Calculation” below) [13].

GFR Calculation

Several formulas can give an estimated GFR. All use information such as:

  • Creatinine levels
  • Cystatin C levels
  • Age
  • Gender

Some formulas use serum creatinine alone; others use serum cystatin C alone. But certain formulas use both, which gives the best GFR estimates [18].

If you have a high GFR, your kidneys are likely working well. Healthy kidneys can filter out all creatinine and cystatin C. If your levels of these two markers are high, your GFR estimate will go down. A low GFR means your kidneys are under strain and not filtering blood as efficiently as they should.

You can use an online GFR calculator, which uses the common formulas, to get a GFR estimate.

Different formulas are used to estimate pediatric GFR, or GFR in children. The most accurate ones use a combination of markers (creatinine, cystatin C, and BUN) [19].

Bottom Line

GFR is an important objective estimate, since people cannot simply tell how well their kidneys are working. You may have no symptoms, especially in the early stages of kidney disease. The sooner you discover kidney problems, the sooner treatment can be started.

Your health care providers also need to know your GFR to prescribe medication correctly. Some medications are filtered out by the kidneys and require dosage adjustments. Others can even damage the kidneys, and you may need to avoid them [11].

High Cystatin C

Causes

Kidney disease or damage is the number one reason for high cystatin C levels, but it’s not the only reason. Most of the time, cystatin C is in careful balance with the enzyme it inhibits. An imbalance can occur with normal aging, due to certain chronic diseases, or as a result of lifestyle factors [6].

Aging

Cystatin C levels normally increase with aging. People over 80 years old have at least 50% higher levels [20].

Osteoporosis

People with osteoporosis have much higher cystatin C levels, which can even be used to detect osteoporosis early on. This is especially important in middle-aged to elderly people, ensuring treatment before the disease causes much damage [21].

Cancer

Cystatin C is higher in people with certain cancers. However, it is unclear whether cystatin C acts to inhibit or promote tumors [22].

Hyperthyroidism & Diabetes

Patients with hyperthyroidism and diabetes have elevated cystatin C levels. Scientists are still trying to understand how and if cystatin C can affect these diseases [10, 10].

Health Effects

Mortality and Heart Complications

According to an analysis of over 38k people, the elderly who had elevated cystatin C were more likely to die from heart-related and any other causes [23].

Cystatin C may also be an alternative way to predict heart-related complications. But it is less sensitive than two other markers: C-reactive protein and natriuretic peptide [24].

Pregnancy Complications

Preeclampsia is a condition that occurs only in pregnancy, causing sudden high blood pressure and protein in the urine. According to an analysis of over 2k women, cystatin C levels can predict whether or not a woman will develop preeclampsia in the third trimester of pregnancy [25, 26].

Ways to Lower Cystatin C

You may be able to modify your diet and lifestyle to lower cystatin C. If your levels are high, you need to help your kidneys work to the best of their capacities.

1) Eat Kidney-Friendly Foods

The first step you can take is to eat a kidney-healthy diet, such as the renal diet. Additionally, the National Kidney Foundation recommends the DASH (Dietary Approaches to Stop Hypertension) diet [27].

2) Exercise

Exercise helps improve kidney function, especially light physical activity on a regular basis [28].

3) Coffee

A small study of healthy volunteers looked at the effect of coffee and green tea on cystatin C levels. Drinking coffee for two weeks decreased cystatin C levels and increased GFR, pointing to improved kidney function [29].

4) Lose Weight

Higher cystatin C is linked to greater body weight. Hence, losing a few pounds if you’re overweight may help bring down your cystatin C levels [30].

5) Stop Smoking

Smoking is associated with higher cystatin C levels. Quitting may help lower your levels, while supporting your overall health [30].

6) Keep Diabetes and Blood Pressure in Check

Both diabetes and high blood pressure can strain the kidneys. Thus, take steps to keep your blood sugar and blood pressure under control. Monitor your blood pressure and sugar levels regularly to prevent sudden spikes in either one [31, 32].

7) Resolve Underlying Inflammation

People with inflammation and high CRP levels also have higher cystatin C levels. Some even consider cystatin C to be a marker of inflammation. If you have high cystatin C along with other markers of inflammation, talk to your doctor to uncover and resolve the underlying causes [30].

Low Cystatin C

Causes and Health Effects

Lower levels of cystatin C in the brain increases the risk of Alzheimer’s disease and nerve damage related to it [6].

People with an underactive thyroid (hypothyroidism) also have lower levels of cystatin C [10].

Cystatin C levels can be low in people with hardened arteries (atherosclerosis) and bulges in large blood vessels (aortic aneurysms) [33].

Limitations and Caveats

Research has investigated cystatin C and its role in kidney function in detail. However, the best approach to measuring GFR has yet to be established. Few studies examined the link between cystatin C and other diseases or lifestyle factors [34].

Irregular Cystatin C Levels?

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