Cystatin C
Cystatin C is a kidney filtration marker produced by all nucleated cells at a constant rate. Unlike creatinine, it is NOT affected by muscle mass, sex, age, or diet — making it more accurate when creatinine is unreliable. Ideal for elderly (low muscle), athletes (high muscle), amputees, or malnourished individuals. Combined creatinine + cystatin C eGFR equations are most accurate. Also predicts cardiovascular risk independent of kidney function.
Cystatin C is a small protein produced by all nucleated cells in your body at a constant rate. It’s freely filtered by the kidneys and almost completely reabsorbed and broken down — not returning to the blood. This makes it an excellent marker of kidney filtration: when kidney function declines, cystatin C accumulates in the blood.
Why does this matter? Unlike creatinine, cystatin C is not significantly affected by muscle mass, age, sex, or diet. This makes it particularly valuable when creatinine might be misleading — in elderly individuals with low muscle mass, bodybuilders with high muscle mass, people with muscle-wasting conditions, or those with unusual diets. In these situations, cystatin C provides a more accurate picture of true kidney function.
Cystatin C can be used alone or combined with creatinine to calculate eGFR. The combined equation is considered more accurate than either marker alone, particularly in borderline cases where precise kidney function assessment matters.
Key Benefits of Testing
Cystatin C shines when creatinine is unreliable. For elderly individuals, athletes, amputees, vegetarians, or anyone with abnormal muscle mass, cystatin C provides kidney function assessment that isn’t skewed by body composition.
This test also helps confirm borderline creatinine results. When creatinine-based eGFR is near the threshold for chronic kidney disease diagnosis, adding cystatin C can clarify whether kidney function is truly impaired — avoiding both missed diagnoses and unnecessary CKD labels.
What Does This Test Measure?
Cystatin C measures the blood concentration of this low-molecular-weight protein. Your lab provides results alongside their reference range, and may also report cystatin C-based eGFR.
How Cystatin C Works as a Kidney Marker
Production: All cells with nuclei produce cystatin C at a relatively constant rate. Production isn’t significantly affected by inflammation, diet, or muscle mass.
Filtration: Cystatin C is freely filtered by the kidney’s glomeruli — it passes easily from blood into the kidney tubules.
Elimination: After filtration, cystatin C is reabsorbed by tubular cells and broken down. It doesn’t return to the blood. This means blood levels depend almost entirely on how well the glomeruli are filtering.
Cystatin C vs. Creatinine
Both markers reflect kidney filtration, but with important differences:
Creatinine:
- Comes from muscle metabolism
- Affected by muscle mass, diet, supplements
- Men have higher values than women
- Widely available, inexpensive
Cystatin C:
- Comes from all nucleated cells
- Not significantly affected by muscle mass
- Similar values in men and women
- Less affected by age
- Less available, more expensive
Using Both Together
The most accurate eGFR equations use both creatinine and cystatin C. When the two markers give similar estimates, confidence is high. When they differ significantly, investigation may reveal why — and the cystatin C-based estimate may be more reliable in certain populations.
Why This Test Matters
Accurate Assessment When Muscle Mass Is Unusual
Creatinine-based eGFR can over- or underestimate kidney function when muscle mass doesn’t match assumptions:
Elderly/frail: Low muscle mass means low creatinine production. Creatinine may appear “normal” even when kidney function is impaired.
Bodybuilders/athletes: High muscle mass means high creatinine production. Creatinine may appear elevated even with normal kidneys.
Amputees: Reduced muscle mass leads to lower creatinine that doesn’t reflect kidney function.
Muscle-wasting diseases: Conditions like muscular dystrophy affect creatinine production.
Cystatin C provides accurate assessment in all these situations.
Confirms Borderline Results
When creatinine-based eGFR is near the cutoff for chronic kidney disease (around 60), adding cystatin C helps determine true kidney status. This matters because a CKD diagnosis affects insurance, medication choices, and patient perception.
Detects Early Kidney Decline
Some studies suggest cystatin C may rise earlier than creatinine in developing kidney disease, potentially detecting problems sooner.
Predicts Cardiovascular Risk
Research shows cystatin C levels predict cardiovascular events and mortality, possibly better than creatinine. This association exists even after accounting for kidney function, suggesting cystatin C may reflect more than just filtration.
Guides Medication Dosing
When accurate kidney function assessment is critical for drug dosing, cystatin C-based eGFR may provide better guidance than creatinine alone.
What Can Affect Your Cystatin C?
Primary Factor: Kidney Function
Kidney filtration is the main determinant of cystatin C levels. As filtration declines, cystatin C rises.
Other Factors (Minor Effects)
Thyroid function:
- Hyperthyroidism may increase cystatin C production
- Hypothyroidism may decrease production
- Effect is relatively small but worth noting
Corticosteroids: High-dose steroids may increase cystatin C independent of kidney function
Inflammation: Some studies suggest very high inflammation might affect levels, though this is debated
Obesity: May slightly elevate cystatin C
Smoking: May slightly elevate cystatin C
Malignancy: Some cancers may affect production
What Does NOT Significantly Affect Cystatin C
Unlike creatinine, cystatin C is not significantly affected by:
- Muscle mass
- Sex
- Age (in adults)
- Dietary protein intake
- Creatine supplements
- Recent exercise
Testing Considerations
No fasting required. No need to avoid exercise before testing. Results are not affected by recent meals. If thyroid disease is present, this should be considered in interpretation.
When Should You Get Tested?
Borderline Creatinine-Based eGFR
When creatinine-based eGFR is near 60 (the threshold for CKD stage 3), cystatin C can confirm whether kidney function is truly reduced.
Unusual Muscle Mass
For elderly, frail, highly muscular, or amputee individuals, cystatin C provides more accurate kidney assessment than creatinine alone.
Discrepancy Between Creatinine and Clinical Picture
If creatinine-based eGFR doesn’t match clinical expectations — for example, a healthy-appearing person with low eGFR, or an ill person with normal creatinine — cystatin C can clarify.
Cardiovascular Risk Assessment
Cystatin C adds prognostic information about cardiovascular risk, particularly in older adults.
Medication Dosing Requiring Precise Kidney Function
For drugs with narrow therapeutic windows that are cleared by kidneys, accurate eGFR from cystatin C may improve dosing.
Monitoring Kidney Function Trends
Serial cystatin C measurements can track kidney function changes, particularly when muscle mass may be changing (weight loss, illness).
Understanding Your Results
Your lab provides reference ranges. Results may include cystatin C-based eGFR:
Within reference range (cystatin C low, eGFR normal): Kidney filtration appears normal. This is particularly reassuring if creatinine-based eGFR was borderline.
Above reference range (cystatin C elevated, eGFR reduced): Suggests reduced kidney filtration. The higher the cystatin C, the lower the kidney function. Interpret with creatinine results — if both agree, confidence is high.
When Creatinine and Cystatin C Disagree
Low creatinine-eGFR but normal cystatin C-eGFR: May indicate high muscle mass falsely elevating creatinine. True kidney function likely normal.
Normal creatinine-eGFR but low cystatin C-eGFR: May indicate low muscle mass masking kidney dysfunction. True kidney function may be reduced.
Significant discrepancy: Consider factors affecting each marker. The cystatin C-based estimate may be more reliable when muscle mass is unusual.
Combined CKD-EPI Equation
The most accurate approach uses both markers together. Labs may report eGFR from creatinine alone, cystatin C alone, or the combined equation. The combined estimate is generally most reliable.
What to Do About Abnormal Results
For Elevated Cystatin C
Confirm kidney dysfunction: Compare with creatinine-based eGFR. If both indicate reduced function, kidney disease is likely.
Evaluate for causes:
- Diabetes — most common cause of CKD
- Hypertension — second most common cause
- Glomerulonephritis, polycystic kidney disease, and others
Check for thyroid dysfunction: If cystatin C is unexpectedly elevated, thyroid function should be assessed.
Protect kidney function:
- Control blood pressure
- Manage diabetes optimally
- Avoid nephrotoxic medications
- Consider ACE inhibitor or ARB if proteinuria present
For Normal Cystatin C When Creatinine Is Elevated
Consider high muscle mass: If the individual is muscular, the creatinine elevation may not indicate kidney disease.
Trust cystatin C: In this scenario, cystatin C-based eGFR is likely more accurate.
Avoid unnecessary CKD diagnosis: Don’t label someone with kidney disease based on creatinine alone when cystatin C is normal.
Follow-Up
Repeat testing confirms persistent abnormalities. Monitor trends over time. Consider nephrology referral for significantly reduced eGFR or unclear etiology.
Related Health Conditions
Chronic Kidney Disease
Progressive Function Loss: Cystatin C accurately stages CKD when creatinine is unreliable. Combined eGFR equations using both markers provide the most accurate assessment for diagnosis and monitoring.
Sarcopenia and Frailty
Muscle Loss in Aging: Elderly individuals with sarcopenia have low creatinine production, masking kidney dysfunction. Cystatin C reveals true kidney function in this population.
Cardiovascular Disease
Risk Prediction: Elevated cystatin C predicts cardiovascular events and mortality independent of traditional risk factors. It may identify high-risk individuals who would be missed by creatinine alone.
Acute Kidney Injury
Early Detection: Some research suggests cystatin C may detect acute kidney injury earlier than creatinine, though this is still being studied.
Thyroid Disorders
Affects Cystatin C: Hyperthyroidism can elevate and hypothyroidism can lower cystatin C independent of kidney function — important for accurate interpretation.
Why Regular Testing Matters
For individuals where creatinine is unreliable, cystatin C provides accurate kidney function monitoring that catches changes standard testing might miss. In elderly patients with declining muscle mass, serial cystatin C measurements track kidney function more accurately than creatinine trends.
As cardiovascular risk marker, cystatin C adds prognostic information beyond kidney function, helping identify high-risk individuals for preventive intervention.
Related Biomarkers Often Tested Together
Creatinine — Traditional kidney marker. Combined with cystatin C for most accurate eGFR.
BUN — Another kidney marker reflecting protein metabolism.
eGFR — Calculated from creatinine, cystatin C, or both.
Urinalysis and Urine Albumin/Creatinine Ratio — Detect kidney damage that filtration markers might miss.
TSH — Thyroid function affects cystatin C; may be checked if results are unexpected.
Note: Information provided in this article is for educational purposes and doesn’t replace personalized medical advice.
Frequently Asked Questions
Cystatin C is a small protein produced by all cells and filtered by the kidneys. Unlike creatinine, it’s not affected by muscle mass, making it a more accurate kidney function marker in many people — especially elderly, muscular, or malnourished individuals.
Creatinine comes from muscle, so muscle mass affects levels. This can make creatinine misleading in elderly people (low muscle), athletes (high muscle), or amputees. Cystatin C production doesn’t depend on muscle, providing more accurate kidney assessment in these groups.
Neither is universally “better” — they’re complementary. Creatinine is widely available and inexpensive. Cystatin C is more accurate when muscle mass is unusual. Using both together in combined eGFR equations provides the most accurate assessment.
Elevated cystatin C indicates reduced kidney filtration — the kidneys aren’t clearing this protein efficiently. This suggests kidney function impairment, though thyroid disorders can also affect levels.
No. Unlike creatinine, cystatin C isn’t affected by recent meals, protein intake, or exercise. No special preparation is needed.
Cost and availability limit widespread use. Cystatin C testing is more expensive than creatinine and not available in all labs. It’s typically reserved for situations where creatinine may be unreliable or when confirmation is needed.
Yes — research shows elevated cystatin C predicts cardiovascular events and death, even after accounting for kidney function. This suggests it may reflect vascular health beyond just kidney filtration.
Cystatin C is typically used for specific indications rather than routine screening. Test when creatinine may be unreliable, to confirm borderline eGFR, or for cardiovascular risk assessment. Frequency depends on clinical situation.
References
Key Sources:
- Inker LA, et al. New creatinine- and cystatin C-based equations to estimate GFR. N Engl J Med. 2021;385(19):1737-1749.
- Shlipak MG, et al. Cystatin C versus creatinine in determining risk based on kidney function. N Engl J Med. 2013;369(10):932-943.
- KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int Suppl. 2013;3(1):1-150.
