Does cystatin C (Cystatin C) supersede Glomerular Filtration Rate (GFR) in assessing kidney function?

Cystatin C Testing vs. GFR in Kidney Function Assessment

Cystatin C does not outrank GFR but serves as a complementary test that can improve GFR estimation accuracy in specific clinical situations. The 2024 KDIGO guidelines recommend using eGFRcr-cys (combined creatinine and cystatin C estimation) in clinical situations when eGFRcr is less accurate and GFR affects clinical decision-making. 1

When to Use Cystatin C vs. Standard eGFR

Primary Use Cases for Cystatin C:

• When creatinine-based eGFR (eGFRcr) is suspected to be inaccurate:
  • Extremes of muscle mass (very low or high)
  • Unusual dietary patterns (vegetarian, high protein)
  • Conditions affecting muscle metabolism
  • Critical clinical decisions where accurate GFR is essential

Algorithm for Cystatin C Testing:

1. Initial Assessment: Use serum creatinine with an estimating equation (eGFRcr) 1
2. Consider Cystatin C when:
   • eGFRcr is 45-59 ml/min/1.73m² without albuminuria 1
   • Patient has conditions affecting muscle mass
   • Discrepancy exists between clinical presentation and eGFRcr
   • Critical treatment decisions depend on precise GFR
3. For highest accuracy: Use combined eGFRcr-cys (both markers together)

Advantages of Cystatin C

• Less affected by non-renal factors than creatinine:
  • Independent of muscle mass, age, sex 1
  • Produced at a constant rate by all nucleated cells 2
  • Not secreted by tubules (unlike creatinine)
• More sensitive for detecting early kidney function decline 2
• Better correlation with measured GFR in certain populations 2
• Improved risk stratification for cardiovascular events and mortality 1

Limitations of Cystatin C

• Limited availability in many clinical laboratories 1
• Higher cost compared to creatinine testing
• Lack of standardized reference calibration in some regions 1
• Can be affected by inflammation, thyroid dysfunction, and certain medications
• Insufficient evidence of effectiveness and cost-effectiveness in routine use 1

Practical Considerations

• The gold standard for GFR measurement remains exogenous filtration marker clearance (inulin, iohexol) 3
• For routine clinical practice, eGFRcr remains the initial test of choice 1
• When cystatin C is measured, it should be accompanied by creatinine measurement on the same sample to enable calculation of eGFRcr-cys 1
• In elderly cancer patients, cystatin C may provide better accuracy for medication dosing 1

Important Caveats

• Neither creatinine nor cystatin C alone should be used without an estimating equation 1
• A single abnormal GFR estimate should not be used to diagnose chronic kidney disease; confirmation of chronicity (>3 months) is required 1
• Laboratory standards for cystatin C measurement are critical for accurate results 1
• The 2024 KDIGO guidelines emphasize that GFR refers specifically to glomerular filtration, while "kidney function" encompasses all kidney functions 1

In summary, cystatin C does not replace GFR but rather provides an alternative or complementary method to estimate it more accurately in specific clinical scenarios where creatinine-based estimates may be unreliable.