Cystatin C is a small protein produced by nearly all cells in the body and released into the bloodstream. It is filtered out of the blood exclusively by the kidneys, making it a valuable indicator of kidney function. Under normal circumstances, your kidneys maintain a stable level of cystatin C in the blood. However, if kidney function begins to decline, cystatin C levels increase, often before other signs of kidney damage become apparent.
The kidneys contain tiny filtering units called glomeruli, which remove waste, excess fluids, and small molecules like cystatin C from the blood. After filtration, cystatin C is reabsorbed and broken down by the kidney’s tubular cells and is not returned to the bloodstream. This process makes cystatin C a reliable marker of how well the kidneys are filtering blood—a function known as the glomerular filtration rate (GFR).
A cystatin C blood test can help estimate your GFR, which is the best overall measure of kidney function. While serum creatinine is more commonly used to estimate GFR, cystatin C may provide a more accurate picture in certain situations—especially when muscle mass, diet, or other factors could skew creatinine-based measurements.
Cystatin C levels are used in a formula—along with age, sex, and sometimes race—to estimate your cystatin C-based GFR (eGFRcys). Some formulas combine both creatinine and cystatin C for an even more accurate assessment, especially in people with borderline or unclear kidney function.
A healthcare provider may order a cystatin C test when:
A previous creatinine-based eGFR is inconclusive or inconsistent with clinical symptoms.
The patient is elderly, overweight, malnourished, or very muscular (e.g., bodybuilders)—situations where creatinine levels may not reflect true kidney function.
There is a need to monitor early kidney dysfunction, especially when subtle changes in GFR could have clinical significance.
Additional confirmation of chronic kidney disease (CKD) is needed before initiating or adjusting treatment.
Unlike creatinine, which is influenced by muscle mass, diet, age, and sex, cystatin C is less affected by these variables, making it a potentially more accurate and consistent measure of kidney function in certain populations. It may also detect mild kidney impairment earlier than creatinine.
Normal kidney function: Cystatin C levels remain stable.
Declining kidney function: GFR decreases, causing cystatin C to accumulate in the blood.
Improving kidney function: GFR increases, allowing cystatin C levels to decline as the kidneys resume proper filtration.
Cystatin C rises in parallel with other kidney function markers such as creatinine and blood urea nitrogen (BUN) when the kidneys are unable to filter effectively.
While the use of cystatin C in estimating GFR is supported by growing research, it is not yet a routine part of all kidney evaluations. Availability may vary between laboratories, and ongoing efforts are being made to standardize cystatin C testing and calibration across clinical settings.
In Summary
The cystatin C blood test is a useful tool for evaluating kidney health and estimating GFR—especially in cases where traditional tests like creatinine might be misleading. It provides a clearer picture in individuals with unusual body composition or when early kidney impairment is suspected. While it is not yet the standard for GFR testing, its use is expanding as evidence grows and testing becomes more accessible.
Ebert N, et al. Cystatin C standardization decreases assay variation and improves assessment of glomerular filtration rate. Clin Chim Acta. 2016.
KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease.
Inker LA, et al. Estimating GFR from serum creatinine and cystatin C. N Engl J Med. 2012.
Waheed S, et al. Combined association of albuminuria and cystatin C-based estimated GFR with mortality and heart disease outcomes. Am J Kidney Dis. 2012.
Dalcomune DM, et al. Predictive value of cystatin C for illness severity in ICU patients. Clin Biochem. 2016.
Brown CS, et al. Cystatin C Falsely Underestimated GFR in a Critically Ill Patient. Case Rep Nephrol. 2016.
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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While most discussions focus on high Cystatin C, low levels can also provide useful information in certain situations:
Low Cystatin C may indicate increased kidney filtration (hyperfiltration), which can occur in early diabetes or during pregnancy.
Hyperfiltration isn’t necessarily a sign of “better” kidney function—it can sometimes precede kidney damage.
Cystatin C is minimally influenced by muscle mass or diet, making it a reliable marker even in people with low muscle mass.
In rare and severe cases of protein-energy malnutrition or cachexia, Cystatin C production may decrease slightly.
Hyperthyroidism (overactive thyroid) is associated with higher Cystatin C levels.
Hypothyroidism (underactive thyroid) is associated with lower Cystatin C levels.
Thyroid status should always be considered when interpreting Cystatin C results.
Corticosteroid medications can increase Cystatin C.
Low Cystatin C might be seen with adrenal insufficiency or low steroid levels, although this effect is less pronounced in clinical practice.
Low Cystatin C levels are usually not a cause for concern on their own. They are best interpreted as part of a broader set of lab results. If your Cystatin C is low but your kidney function is otherwise normal, and there are no signs of malnutrition or thyroid disease, it’s typically not clinically significant.
Recent research suggests that very low Cystatin C could, in some cases, be linked to increased kidney filtration and possibly long-term risk, but these findings are still being studied and are not yet part of routine clinical decision-making.
Review other kidney health markers (creatinine, eGFR, BUN).
Consider thyroid function tests (TSH, Free T4) if there are symptoms or concerns.
Discuss your results with your doctor, who can interpret them in the context of your overall health.
Summary Table: Key Factors Affecting Cystatin C
| Factor | Effect on Cystatin C | Notes |
|---|---|---|
| Hyperfiltration | Low | Early diabetes, pregnancy |
| Severe malnutrition | Slightly low (rare) | Usually minimal effect |
| Hyperthyroidism | High | Raises Cystatin C |
| Hypothyroidism | Low | Lowers Cystatin C |
| Glucocorticoid deficiency | Low (possible) | Less established |
In summary: Low Cystatin C is rarely a problem by itself and is best understood as one piece of your overall health picture. Always consult your healthcare provider for personalized interpretation.
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0.52 - 1.27 mg/L.