Cystatin C is a protein found in the blood that indicates how well the kidneys are functioning. Measuring its concentration provides clinicians with a precise tool for evaluating the glomerular filtration rate (GFR), the primary measure of kidney health. This measurement is important for the early detection and proper staging of chronic kidney disease (CKD), allowing for timely intervention and management.
The Basics of Cystatin C
Cystatin C is a small protein produced constantly by nearly all nucleated cells throughout the body. Its function is to act as a protease inhibitor, regulating enzymes that break down proteins. Due to its small size, Cystatin C is freely filtered out of the bloodstream by the glomeruli, the kidney’s filtering units.
Once filtered, the protein is completely reabsorbed and broken down by the cells of the proximal renal tubules. A healthy kidney efficiently removes this protein, maintaining a stable concentration in the blood. If kidney function declines, however, the blood concentration of Cystatin C begins to rise.
The Clinical Advantage of Cystatin C Testing
Measuring Cystatin C offers an advantage over the traditional marker, serum creatinine, in assessing kidney function. Serum creatinine is a waste product of muscle metabolism, meaning its levels are influenced by a person’s muscle mass, diet, sex, and age. These non-kidney factors can make creatinine-based estimates of GFR less reliable.
Cystatin C production is stable across individuals, making its blood level less affected by muscle mass, body size, or protein intake. This stability provides a more precise and reliable estimate of the glomerular filtration rate. For example, creatinine levels may appear normal in elderly or malnourished individuals despite significant kidney impairment, masking early disease.
Conversely, in muscular individuals, creatinine levels can be misleadingly high, suggesting kidney issues that do not exist. Using Cystatin C is valuable in these situations, as it offers a clearer picture of kidney filtration capacity. The test is also more sensitive than creatinine in detecting mild or early kidney disease.
Understanding Your Results
Cystatin C levels are used to calculate the Estimated Glomerular Filtration Rate (eGFR), the most accepted index of overall kidney function. The eGFR calculation uses the measured Cystatin C concentration, along with factors like age and sex, to estimate how many milliliters of blood the kidneys clean per minute. The relationship is inverse: as the blood concentration of Cystatin C increases, the calculated eGFR decreases, indicating a decline in filtration capacity.
A result is reported in milliliters per minute per 1.73 square meters (\(\text{mL/min/1.73 m}^2\)) of body surface area. An eGFR of 60 or higher is considered within the healthy range, while a persistent eGFR below 60 suggests chronic kidney disease (CKD). CKD is staged based on the eGFR result, with Stage 3 corresponding to an eGFR between 30 and 59, and Stage 4 falling between 15 and 29.
An eGFR below 15 indicates Stage 5 CKD, or kidney failure, which requires dialysis or a transplant. Because Cystatin C is a more stable marker, the eGFR derived from it provides accurate risk prediction for adverse outcomes like progression to end-stage kidney disease and cardiovascular events.
Non-Kidney Factors Affecting Levels
While Cystatin C is a more reliable marker than creatinine, its levels are not exclusively determined by kidney function. Certain conditions and medications can cause fluctuations in the protein’s blood concentration. For instance, thyroid dysfunction can affect the result, with hyperthyroidism tending to lower Cystatin C levels and hypothyroidism causing them to rise.
Systemic inflammation is associated with higher Cystatin C concentrations, independent of the kidneys’ filtering ability. Some medications, such as corticosteroids, can increase the protein’s production, leading to a falsely elevated reading. Obesity and poorly controlled diabetes have also been linked to higher levels of Cystatin C.
Clinicians must consider these confounding factors when interpreting the results. Despite these influences, Cystatin C remains a valuable tool, often used in combination with creatinine and urine albumin measurements to provide a comprehensive assessment of kidney health.