When should cystatin C (Cystatin C) be used to calculate Glomerular Filtration Rate (GFR) in patients with Chronic Kidney Disease (CKD)?

When to Use Cystatin C to Calculate GFR in CKD

Cystatin C should be used to calculate GFR primarily as a confirmatory test in adults with eGFRcreat 45-59 ml/min/1.73 m² who do not have markers of kidney damage (such as albuminuria) when confirmation of CKD diagnosis is required. 1, 2

Primary Indications for Cystatin C Testing

Confirmatory Testing

• Use cystatin C when eGFRcreat is 45-59 ml/min/1.73 m² without albuminuria
• If eGFRcys or eGFRcreat-cys is also <60 ml/min/1.73 m², CKD diagnosis is confirmed
• If eGFRcys or eGFRcreat-cys is ≥60 ml/min/1.73 m², CKD diagnosis is not confirmed

Clinical Scenarios with Non-GFR Determinants of Creatinine

According to the 2024 KDIGO guidelines, cystatin C should be used in specific clinical circumstances where creatinine-based eGFR is less accurate due to non-GFR determinants 1:

1. Body habitus and muscle mass abnormalities:

   • Eating disorders
   • Extreme athletes/bodybuilders
   • Above-knee amputations
   • Spinal cord injuries with para/quadriplegia
   • Class III obesity (combined creatinine-cystatin C equation is most accurate)

2. Dietary factors:

   • Low-protein diets
   • Ketogenic diets
   • Vegetarian diets
   • High-protein diets and creatine supplements

3. Comorbid conditions:

   • Malnutrition (consider measured GFR for critical treatment decisions)
   • Cancer (combined equation demonstrated to be most accurate)

Laboratory Implementation

When implementing cystatin C testing, laboratories should 1:

• Measure cystatin C using assays with calibration traceable to international standard reference materials
• Report eGFRcys and eGFRcreat-cys in addition to serum cystatin C concentration
• Round eGFR to the nearest whole number relative to body surface area of 1.73 m²
• Flag eGFR levels <60 ml/min/1.73 m² as decreased

Clinical Decision Algorithm

1. Initial Assessment:

   • Use serum creatinine and eGFRcreat for initial assessment 1
   • Understand clinical settings where eGFRcreat is less accurate

2. When to Add Cystatin C:

   • If eGFRcreat is 45-59 ml/min/1.73 m² without albuminuria
   • If patient has conditions affecting muscle mass or creatinine production
   • If more accurate GFR assessment will impact treatment decisions

3. Interpretation:

   • If both eGFRcreat and eGFRcys are <60 ml/min/1.73 m², confirm CKD diagnosis
   • If eGFRcys or eGFRcreat-cys is ≥60 ml/min/1.73 m² in a patient with eGFRcreat 45-59 ml/min/1.73 m², CKD is not confirmed

Caveats and Pitfalls

• Cystatin C also has non-GFR determinants that can affect its accuracy, including smoking and certain inflammatory conditions 1
• The combined creatinine-cystatin C equation (eGFRcreat-cys) generally provides the most accurate estimate of GFR 1
• In transplant recipients, the KDIGO recommendation for using cystatin C as a confirmatory test may still result in misclassification of CKD in some patients 1
• Consider measured GFR using exogenous filtration markers when more accurate GFR determination will significantly impact treatment decisions 1

Special Considerations

• In pediatric patients, different considerations apply for GFR estimation and laboratory standards 1
• Race-based adjustments in GFR estimation should be avoided; adding cystatin C to creatinine improves accuracy of race-neutral equations 1, 2
• For elderly patients, malnourished patients, or those with extremes of body size, cystatin C testing may provide more reliable GFR estimates 2