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 protein that inhibits the breakdown of other proteins. It is produced by most cells in the body and can be found in all bodily fluids [1, 2, 3].
This protein plays a variety of roles: it’s involved in growth, bone metabolism, and studies suggest it protects the brain against injury and some neurodegenerative diseases [4, 5].
Cystatin C is almost completely broken down in the kidneys (>99%). In healthy people, both the production and the breakdown of this protein happen at a relatively constant rate. But if your kidneys are not working properly, cystatin C builds up in the blood [6, 7, 8]. That is why this molecule can tell us how well our kidneys are working.
Because kidney function is tightly interwoven with the function of other organs in the body, studies suggest that higher cystatin may also predict a higher risk of heart disease, cognitive dysfunction, and all-cause mortality [9, 10, 11].
On the other hand, researchers found that lower levels may be associated with an increased risk of Alzheimer’s and aneurysms [4, 12, 13].
Cystatin C Test
Normal Range
The normal range of cystatin C is around 0.62 – 1.15 mg/L. Values can vary between laboratories. Generally, higher cystatin C levels point to poor kidney function [7].
Advantages and Disadvantages over Creatinine
Pros
Cystatin C can be used as a replacement for blood creatinine for the assessment of kidney function.
It has several advantages over creatinine:
- Its levels don’t depend on muscle mass, physical activity, or protein intake. That’s why it can be used in people who lost muscle mass, such as the elderly and people with chronic disease (e.g. heart failure, liver cirrhosis, and AIDS) [6, 14, 9, 15].
- It can detect mild decreases in kidney function, known as “preclinical kidney dysfunction”. Creatinine, on the other hand, doesn’t increase until 50% of kidney function is lost [14, 15, 16].
- It rises faster than creatinine, and therefore it can detect kidney injury faster [7, 6, 17]
Cons
Studies have found that there are factors that can affect cystatin C level regardless of the kidney function:
- Inflammation [13, 18]
- Thyroid issues (either low or high levels of thyroid hormones) [4]
- Corticosteroid medication [4, 19, 18]
- Cancer [6, 4, 20, 21, 22]
- Chemotherapy [23]
- Aging [24, 4]
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 [25].
Because neither cystatin C nor creatinine is perfect, sometimes they are both combined to access kidney function. Cystatin C is often used with creatinine to estimate GFR [9, 26].
Blood urea nitrogen (BUN), a breakdown product of protein metabolism, is also used to measure how well the kidneys are working [27].
High Cystatin C
Higher than normal cystatin C levels mean that kidney function is likely reduced. Your doctor will interpret this test, taking into account your medical history, symptoms, and other tests.
Causes
Causes shown below are commonly associated with high cystatin C. Work with your doctor or another health care professional to get an accurate diagnosis.
The most common cause of high cystatin C levels is impaired kidney function, which can happen in various diseases, or a result of drugs such as chemotherapeutics [14, 15, 28].
Other factors that can slightly increase cystatin C include:
- Chronic inflammation (in conditions such as lupus, liver disease, obstructive sleep apnea, lung disease, Parkinson’s, and HIV) [29, 30, 9, 15, 31, 32, 33, 34, 35, 36, 37, 38, 39]
- Obesity [40, 15]
- Physical inactivity and prolonged bed rest [41]
- Smoking [9, 42, 43]
- Alcohol [9]
- Hyperthyroidism [44, 45, 46, 47]
- Growth hormone excess (acromegaly) [48]
- Some types of cancer (e.g. multiple myeloma) [49, 6, 4, 20, 21, 22]
- Medication such as corticosteroids, fenofibrate (but not other fibrates), and chemotherapeutics [15, 4, 19, 18, 50, 23]
- Third trimester in pregnancy and twin pregnancies overall [51, 52]
- Genetics [53]
- Aging [15, 43]
High Cystatin C in Disease
Studies have found an association between higher cystatin C levels and:
- High blood pressure [15, 14]
- Metabolic syndrome [54, 55]
- Pre-diabetes and diabetes [15, 56, 57]
- Hardening of the arteries (atherosclerosis) [13, 58, 59, 60]
- Heart disease [9, 14, 61, 62, 63]
- A decline in cognitive function, dementia, and Alzheimer’s [4, 12, 64]
- Depression [65, 66]
- Frailty, worse exercise capacity and reduced mobility [67, 68, 69]
- Lower bone mineral density, osteoporosis, and fractures [15, 70, 71, 72, 73]
- Preeclampsia in pregnancy [51]
- All-cause and heart disease-associated mortality [69, 74, 75, 76, 10, 11, 61, 77, 78, 63]
Keep in mind, these studies have looked at association, not causation. Higher cystatin C levels are likely not causing any of these conditions. Instead, it’s possible that underlying conditions such as chronic inflammation or impaired kidney function increase cystatin C and also play a role in the conditions listed above.
Lowering Cystatin C
The most important thing is to work with your doctor to find out what’s causing your high cystatin C and to treat any underlying conditions, such as kidney disease, high blood pressure, diabetes, HIV, or cancer. Studies have shown that cystatin C decreases with appropriate therapy [79, 49, 80, 30].
Additional lifestyle changes listed below are other things you may want to discuss with your doctor. None of these strategies should ever be done in place of what your doctor recommends or prescribes!
Diet
If you have kidney issues, eat a kidney-healthy diet (renal diet), high in fruits and vegetables, and lower in protein and potassium which kidneys have a harder time processing [81].
Additionally, the National Kidney Foundation recommends the DASH (Dietary Approaches to Stop Hypertension) diet [81].
Mediterranean diet has also been linked to lower cystatin C levels [82]. It may be a suitable choice for those with only mildly impaired kidney function. Discuss it with your doctor.
Lifestyle
Exercise helps improve kidney function, especially light physical activity on a regular basis. Studies have shown that seniors with stronger muscles have better kidney function [83, 84].
Lose weight if overweight. It may help bring down your cystatin C levels [85].
Smoking is associated with higher cystatin C levels. Quitting may help lower your levels, while supporting your overall health [85].
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 [86, 87].
Finally, your mindset matters. An interesting study has found that feeling older than you are can increase your cystatin C levels (along with other adverse health outcomes). Staying mentally, physically, and socially active can help you feel younger and age better [88, 89, 90, 91].
Low Cystatin C
Causes
Causes shown below have been associated with low cystatin C. Work with your doctor or another health care professional to get an accurate diagnosis. Your doctor will interpret this test, taking into account your medical history, symptoms, and other test results.
Initial studies suggest these may decrease cystatin C:
- Hypothyroidism [44, 45, 46, 92]
- Prolonged broadband noise exposure (e.g. from jet engines) [93]
- Kawasaki disease (blood vessel inflammation in children) [94]
- Neuromyelitis optica spectrum disorders (inflammatory disorders of the nervous system) [95]
- Bladder cancer [96]
- Genetics [97, 53]
Low Cystatin C in Disease
Lower cystatin C levels have been associated with a higher risk of:
- Cognitive dysfunction and Alzheimer’s disease [4, 97, 98]
- Hardening of the arteries (atherosclerosis) [13, 9]
- Aneurysms [13, 99]
Cystatin C’s role is to break down other proteins. It’s possible that when there is less cystatin C, some proteins don’t get broken down efficiently, causing issues in the body.
For example, in a study that followed over 1.9k seniors (>70) over 11 years, lower cystatin C was associated with a higher risk of developing Alzheimer’s disease, independently of age, APOE4 genotype, diabetes, and other risk factors. A 0.1-μmol/L decrease of cystatin C between ages 70 and 77 was associated with a 29% higher risk of incident Alzheimer’s disease [98].
Increasing Cystatin C
The most important thing is to work with your doctor to find out what’s causing your low cystatin C and to treat any underlying conditions.
In addition, it may be of benefit to monitor your blood vessel and brain health. These can help your blood vessel and brain health:
- Staying physically, mentally, and socially active
- Avoiding tobacco and excess alcohol
- Consuming a healthy diet
- Maintaining a healthy weight
Scientists are still learning about the importance of cystatin C and its function in the body. Stay tuned, we will update the post with new information as soon as it becomes available.
