Cystatin C is Measured in Blood, Not Urine, for GFR Assessment
Cystatin C is measured in blood (serum), not urine, for assessing kidney function and estimating glomerular filtration rate (GFR). 1
Understanding Cystatin C as a GFR Marker
Cystatin C is an endogenous filtration marker with several advantages over traditional markers:
- Cystatin C is a nonglycosylated basic protein produced at a constant rate by all nucleated cells in the body 2
- It is freely filtered by the renal glomeruli and primarily catabolized in the tubules (not secreted or reabsorbed as an intact molecule) 2
- Unlike creatinine, serum cystatin C concentration is relatively independent of age, sex, and muscle mass, making it potentially more accurate for GFR estimation 2, 3
Clinical Use of Cystatin C in GFR Estimation
The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend using serum cystatin C in specific clinical scenarios:
- As a confirmatory test in adults with creatinine-based eGFR (eGFRcr) of 45-59 mL/min/1.73 m² who do not have markers of kidney damage 1
- When more accurate assessment of kidney function is needed for clinical decision-making 1
- For improved risk stratification of patients with chronic kidney disease 1
Advantages of Cystatin C Over Creatinine
Cystatin C offers several benefits compared to creatinine for GFR estimation:
- Higher sensitivity (93.4%) than serum creatinine (86.8%) for detecting impaired renal function 2
- Earlier detection of declining kidney function - cystatin C levels start to increase when GFR falls below 88 mL/min/1.73 m², while creatinine begins to increase only when GFR falls below 75 mL/min/1.73 m² 2, 4
- Less influenced by non-renal factors like muscle mass and diet that affect creatinine levels 3, 5
Laboratory Standards for Cystatin C Measurement
When measuring cystatin C, clinical laboratories should follow these standards:
- Measure serum cystatin C using an assay with calibration traceable to the international standard reference material 1
- Report serum cystatin C concentration rounded to the nearest 100th of a whole number when expressed in mg/L 1
- Report eGFR from cystatin C (eGFRcys) and combined creatinine-cystatin C (eGFRcr-cys) in addition to the serum cystatin C concentration 1
- Round eGFRcys and eGFRcr-cys to the nearest whole number and express relative to a body surface area of 1.73 m² 1
- Flag eGFRcys and eGFRcr-cys levels less than 60 mL/min/1.73 m² as "decreased" 1
Clinical Considerations and Limitations
While cystatin C is valuable for GFR estimation, clinicians should be aware of certain limitations:
- Cystatin C is more expensive than creatinine testing, which may impact resource allocation 1, 4
- Non-GFR determinants can affect cystatin C levels, including thyroid dysfunction and steroid use 6
- Standardization of cystatin C assays is essential for accurate results - only assays traceable to international standard reference materials should be used 1, 4
Conclusion
For accurate assessment of kidney function, particularly glomerular filtration rate, cystatin C should be measured in blood (serum), not urine. When used appropriately, it provides valuable complementary or alternative information to creatinine-based GFR estimates, especially in patients for whom creatinine may be less reliable.