What is the role of Cystatin C (CysC) in assessing renal function?

From the Guidelines

Cystatin C is a valuable biomarker for assessing renal function, offering several advantages over traditional creatinine-based measurements, and its use is recommended, especially in combination with creatinine, for confirming eGFR in adults at risk for or with chronic kidney disease, as stated in the 2023 guidelines 1.

Key Points About Cystatin C

• Cystatin C is a small protein produced at a constant rate by all nucleated cells in the body and freely filtered by the glomeruli, making it an excellent indicator of glomerular filtration rate (GFR) 1.
• Unlike creatinine, Cystatin C levels are less influenced by muscle mass, age, gender, or diet, providing a more accurate assessment of kidney function across diverse patient populations 1.
• Cystatin C can detect early kidney dysfunction before changes in serum creatinine become apparent, allowing for earlier intervention in declining renal function 1.
• In clinical practice, Cystatin C is often used in combination with creatinine in equations to estimate GFR, such as the CKD-EPI Cystatin C equation, which provides improved accuracy compared to creatinine-based formulas alone 1.
• The measurement requires a simple blood test, and results are typically reported in mg/L, with normal values generally ranging from 0.5 to 1.0 mg/L, though reference ranges may vary by laboratory 1.

Clinical Use of Cystatin C

• Combining filtration markers (creatinine and cystatin C) is more accurate and would support better clinical decisions than either marker alone, as recommended by the 2022 task force on reassessing the inclusion of race in diagnosing kidney disease 1.
• Cystatin C is recommended for confirmatory testing in specific circumstances when eGFR based on serum creatinine is less accurate, such as in individuals with low muscle mass 1.
• Clinical laboratories that measure cystatin C should use an assay with calibration traceable to the international standard reference material and report eGFR from serum cystatin C in addition to the serum cystatin C concentration in adults, specifying the equation used whenever reporting eGFRcys and eGFRcreat-cys 1.

From the Research

Role of Cystatin C in Assessing Renal Function

• Cystatin C (CysC) is a promising marker for assessing renal function, particularly in cases where serum creatinine is not accurate enough 2.
• CysC is less influenced by factors other than glomerular filtration rate (GFR) compared to creatinine, making it a more accurate marker of renal function 2, 3.
• Equations for estimating GFR from CysC values have been developed, making it easier to interpret and use in clinical settings 2.

Cystatin C in Acute Kidney Injury

• CysC has shown promising results in detecting acute kidney injury (AKI), particularly in the early stages 4, 5.
• A rise in CysC concentration of more than 10% from baseline is considered indicative of AKI 4.
• CysC is a better marker of renal function in early stages of AKI and predictive of persistent AKI on colistin treatment 4.

Diagnostic Accuracy of Cystatin C in Chronic Kidney Disease

• Serum CysC has been shown to be a relatively accurate marker for evaluating renal function in chronic kidney disease (CKD) 6.
• The diagnostic odds ratio (DOR) of CysC in predicting CKD was 40, with a sensitivity and specificity of 0.85 and 0.87, respectively 6.
• The area under the curve for the receiver-operating characteristic (AUROC) of CysC to predict CKD was 0.92 6.

Clinical Applications of Cystatin C

• CysC is a useful biomarker for renal function and may be the method of choice in a range of clinical situations, from GFR surveillance in diabetics to the assessment of acute kidney injury in critically ill patients 3, 5.
• CysC could be an important tool to recognize early renal dysfunction and identify renal recovery while on continuous renal replacement therapy (CRRT) in critically ill patients 5.