Cystatin C is a small protein produced constantly by nearly all nucleated cells throughout the human body. Its primary biological function is to act as a potent inhibitor of certain cysteine proteinases, enzymes involved in various cellular processes. This protein is secreted into the bloodstream at a steady rate, making its concentration stable and reliable. This stability and consistent production profile have made it a valuable tool in medical diagnostics, providing physicians with an important measure for assessing organ function.
The Biological Role of Cystatin C
Cystatin C is a low-molecular-weight protein (approximately 13,000 Daltons) that passes easily through the kidney’s filtration barrier. It is produced continuously by all nucleated cells, contributing to its stable concentration in the plasma. It is freely filtered out of the blood by the glomeruli.
After filtration, the protein is nearly completely reabsorbed by the proximal renal tubules. Within these tubular cells, Cystatin C is entirely broken down and metabolized, meaning virtually none of the original protein is returned to the bloodstream or excreted in the urine.
Because Cystatin C production is constant, its concentration in the blood directly reflects how efficiently the glomeruli are filtering. When filtration slows down, the protein accumulates, leading to a measurable rise in its serum concentration. This makes it a precise marker for the overall filtration capacity of the kidneys.
A Superior Marker for Glomerular Filtration Rate
The core clinical utility of Cystatin C lies in its use to estimate the Glomerular Filtration Rate (GFR). GFR is the standard metric for assessing kidney health, measuring how much blood the kidneys filter per minute. Because Cystatin C is produced stably and is freely filtered, its serum level can be mathematically converted into an estimated GFR (eGFR) value.
This conversion relies on specific formulas, such as the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Cystatin C equation. These equations use the measured concentration, along with a patient’s age and sex, to provide an accurate estimate of the GFR. A normal eGFR value is typically above 90 milliliters per minute per 1.73 square meters of body surface area.
Cystatin C is valuable because it is an endogenous substance, naturally produced by the body. This avoids the need for complex tests requiring the injection of an external filtration marker.
The most accurate assessment often uses a combined equation with both Cystatin C and the traditional marker, creatinine. This two-biomarker approach helps mitigate the non-kidney-related influences that affect each marker individually. This combined measurement provides the most robust picture of a patient’s true kidney function.
Why Cystatin C Outperforms Creatinine
Cystatin C addresses limitations inherent in the traditional marker, serum creatinine. Creatinine is a waste product of muscle metabolism, heavily influenced by muscle mass. Individuals with very high or very low muscle mass, such as the frail elderly, can have misleading creatinine results.
The independence of Cystatin C from muscle mass, diet, and sex provides a major advantage. Unlike creatinine, Cystatin C production remains stable regardless of factors like meat intake or muscle wasting. This stability makes it a more reliable indicator of true kidney function in people whose body composition is unusual.
Cystatin C is also more sensitive in detecting subtle declines in kidney function. Studies suggest that Cystatin C levels may begin to rise earlier than creatinine, signaling impairment when the GFR is still relatively high. This early detection capability allows for earlier intervention in chronic kidney disease.
The speed at which Cystatin C levels change makes it superior for monitoring dynamic kidney function. In acute kidney injury, Cystatin C levels equilibrate more quickly than creatinine. This quicker reflection of functional change provides physicians with more timely and actionable information.
Understanding Your Cystatin C Test Results
The result of a Cystatin C blood test is typically reported as a concentration in milligrams per liter (mg/L). Normal reference ranges for adults generally fall between approximately 0.53 and 1.03 mg/L, though they vary slightly between laboratories. A result is interpreted inversely to kidney function; a higher Cystatin C level signifies a lower estimated GFR.
An elevated level of Cystatin C indicates that the kidneys are not filtering waste efficiently. For example, a result above 1.2 mg/L strongly suggests impaired kidney function. Physicians use this elevated concentration to calculate the eGFR, which determines the stage of any potential chronic kidney disease.
The test is particularly useful where the diagnosis of kidney disease is uncertain or borderline. Guidelines often recommend measuring Cystatin C to confirm chronic kidney disease in patients whose creatinine-based eGFR falls into the mild-to-moderate impairment range (typically 45 to 59 mL/min/1.73m²). Using Cystatin C as a confirmatory test prevents misdiagnosis where creatinine alone might be misleading.
Elevated Cystatin C levels have also been independently associated with an increased risk for cardiovascular disease and all-cause mortality. This suggests the protein may serve as a broader marker of overall health and inflammation, beyond its role as a kidney biomarker. Physicians interpret the result within the context of a patient’s entire medical history.