When is the Cystatin C test recommended for assessing kidney function?

When to Use Cystatin C Testing for Kidney Function Assessment

Cystatin C testing is recommended primarily as a confirmatory test when eGFR based on serum creatinine is less accurate, particularly in adults with eGFR 45-59 ml/min/1.73 m² who do not have markers of kidney damage and require confirmation of CKD diagnosis. 1

Primary Indications for Cystatin C Testing

• Confirmation of CKD diagnosis: When eGFRcreat is 45-59 ml/min/1.73 m² without albuminuria or other markers of kidney damage 1
• Situations where creatinine-based eGFR is less accurate:
  • Individuals with low muscle mass 1
  • Elderly patients 1
  • Malnourished or cachectic patients 1
  • Patients with extremes of body size 1

Benefits of Cystatin C Testing

• More accurate GFR estimation: Cystatin C is produced at a constant rate by all nucleated cells, freely filtered by glomeruli, and not secreted by renal tubules 2
• Independence from non-renal factors: Unlike creatinine, cystatin C is not affected by muscle mass, age, or gender 1, 2
• Earlier detection of kidney dysfunction: Cystatin C can detect decreased GFR at earlier stages (when GFR is around 88 ml/min/1.73 m²) compared to creatinine (which begins to increase when GFR is around 75 ml/min/1.73 m²) 2
• Improved risk stratification: Cystatin C provides better prediction of adverse outcomes including cardiovascular events and mortality in patients with kidney disease 3

Recommended Testing Approach

1. Initial assessment: Use serum creatinine and a GFR estimating equation (preferably 2021 CKD-EPI equation without race variable) 1

2. When to add cystatin C:

   • For confirmatory testing when eGFRcreat is 45-59 ml/min/1.73 m² without albuminuria 1
   • When more accurate GFR assessment will impact treatment decisions 1
   • In patients where creatinine-based estimates are unreliable 1

3. How to use cystatin C results:

   • If eGFRcys or eGFRcreat-cys is also <60 ml/min/1.73 m², CKD diagnosis is confirmed 1
   • If eGFRcys or eGFRcreat-cys is ≥60 ml/min/1.73 m², CKD is not confirmed 1

Clinical Implementation Considerations

• Request both measurements: When ordering cystatin C, request both eGFRcys (cystatin C-based) and eGFRcreat-cys (combined creatinine and cystatin C) for comprehensive assessment 1

• Laboratory considerations: Ensure the laboratory:

  • Uses assays with calibration traceable to international standard reference material 1
  • Reports eGFRcys and eGFRcreat-cys in addition to serum cystatin C concentration 1
  • Uses the CKD-EPI cystatin C equation when available 1

• Limitations to consider:

  • Limited availability in some clinical settings 4
  • Higher cost compared to creatinine testing 5
  • Potential non-GFR determinants of cystatin C levels (inflammation, thyroid dysfunction, certain medications) 3

Special Populations

• Diabetes patients: Cystatin C may detect kidney dysfunction at an earlier stage than creatinine in people with diabetes 1

• Elderly cancer patients: Cystatin C may be superior for drug dosing calculations in elderly cancer patients, particularly for drugs like carboplatin and topotecan 1

• Race considerations: Adding cystatin C to serum creatinine improves the accuracy of race-neutral eGFR equations, addressing concerns about race-based adjustments in kidney function assessment 1

By following these guidelines for cystatin C testing, clinicians can more accurately assess kidney function, improve CKD diagnosis, and better predict patient outcomes, particularly in populations where creatinine-based estimates are less reliable.