What is cystatin C (Cystatin C)?

From the Guidelines

Cystatin C is a low molecular weight protein that serves as a reliable biomarker for kidney function, offering a more accurate estimate of glomerular filtration rate (GFR) compared to creatinine, especially in certain populations such as children, the elderly, or those with reduced muscle mass. It is produced by nearly all cells in the body and is filtered by the kidneys, making it a useful indicator of kidney function 1. Unlike creatinine, cystatin C levels are less affected by muscle mass, age, gender, or diet, which can make it a more reliable indicator in certain clinical situations 1.

Key Characteristics of Cystatin C

• It is a low molecular weight protein that is almost completely filtered by the glomerulus 1
• It is not excreted or absorbed by the renal tubules 1
• It is not affected by muscle mass, age, or gender 1
• Normal values for cystatin C are high in infants but approach normal adult levels (0.51-0.98 mg/L) by 1 year of age 1
• A cystatin C level of 1.06 mg/L predicted a GFR <80 mL/min/1.73 m² with a sensitivity and specificity of 91% and 81%, respectively, in a pediatric cohort 1

Clinical Utility of Cystatin C

• Cystatin C testing is particularly useful when standard creatinine-based estimates might be inaccurate 1
• It can detect early kidney dysfunction before changes in creatinine become apparent 1
• The test requires a simple blood draw, and results are typically reported in milligrams per liter (mg/L), with normal adult values generally ranging from 0.5 to 1.0 mg/L 1
• Higher levels suggest decreased kidney function 1
• The use of cystatin C-based estimated glomerular filtration rate (eGFRcys) is considered in specific circumstances, as noted in the KDIGO 2024 clinical practice guideline for the evaluation and management of CKD 1.

From the Research

Definition and Properties of Cystatin C

• Cystatin C is a nonglycosylated basic protein produced at a constant rate by all investigated nucleated cells 2.
• It is freely filtered by the renal glomeruli and primarily catabolized in the tubuli, not secreted or reabsorbed as an intact molecule 2.
• Cystatin C is produced in the nucleated cells in a constant amount, and its serum concentration does not depend on muscle mass and protein intake 3.

Cystatin C as a Marker of Kidney Function

• Cystatin C has been shown to be a reliable and accurate marker of kidney function across diverse populations 4.
• It is superior to creatinine as a marker of kidney function, especially in the early stages of chronic kidney disease 3.
• Cystatin C can be used to estimate glomerular filtration rate (GFR) and is useful in detecting mild reductions in GFR 2.
• Several formulas are available for calculating the GFR from serum cystatin C 3.

Clinical Considerations and Advantages

• The 2012 Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommended using cystatin C to confirm the diagnosis of chronic kidney disease (CKD) and to estimate kidney function when accurate eGFR estimates are needed for clinical decision-making 4.
• Cystatin C has significant advantages as a kidney function marker, including its use in the creatinine "blind" area, in pediatric and the elderly population 3.
• Higher cystatin C concentrations in the general population are associated with an increased cardiovascular risk, as well as with preeclampsia in pregnant women 3.
• Cystatin C could be used as a marker for cardiovascular risk assessment, in predicting and detecting preeclampsia, in patients with malignant diseases, etc. 3.

Laboratory Measurement and Interpretation

• Cystatin C may be determined in the serum, plasma, capillary blood, and urine 3.
• The laboratory methods mainly used to determine its level are nephelometric and turbidimetric immunoassays 3.
• The level of cystatin C should be interpreted carefully because there are factors that can affect its level regardless of renal function (thyroid dysfunction, glucocorticoids use, malignancies, etc.) 3.