Blood Tests for Measuring GFR Beyond BUN and Creatinine
The most important blood test beyond creatinine for measuring GFR is serum cystatin C, which should be used in combination with creatinine (eGFRcr-cys) when creatinine-based estimates are inaccurate and clinical decisions depend on accurate GFR assessment. 1
Primary Alternative: Cystatin C
Cystatin C is the key alternative blood biomarker for GFR estimation and offers several advantages over creatinine alone:
- Cystatin C is produced by all nucleated cells and is less influenced by muscle mass, diet, age, sex, and race compared to creatinine 1, 2
- The combined creatinine-cystatin C equation (eGFRcr-cys) provides the most accurate GFR estimates, with 89% of estimates within 30% of measured GFR compared to 85% for creatinine alone 3
- KDIGO 2024 guidelines strongly recommend using eGFRcr-cys (Grade 1C recommendation) when creatinine-based estimates are less accurate and GFR affects clinical decision-making 1
When to Use Cystatin C
Measure cystatin C in these specific clinical situations where creatinine-based eGFR is unreliable: 1
- Extremes of muscle mass (very low or very high muscle mass, sarcopenia, bodybuilders)
- Extremes of body size (Class III obesity with BMI >40 kg/m²)
- Dietary factors (vegetarian diet, low-protein diet, high-protein diet, creatine supplementation)
- Chronic illness (malnutrition, cancer, heart failure, cirrhosis, muscle wasting diseases)
- Medications affecting creatinine (trimethoprim, cimetidine, anabolic steroids)
- Critical drug dosing decisions (chemotherapy, other nephrotoxic medications)
Important Caveats for Cystatin C
Cystatin C has its own limitations that must be recognized: 1
- High inflammation states can elevate cystatin C independent of GFR
- High catabolic states affect cystatin C accuracy
- Exogenous steroid use influences cystatin C levels
- Thyroid dysfunction can alter cystatin C concentrations
Beyond Blood Tests: Measured GFR
When even eGFRcr-cys is thought to be inaccurate, measure GFR directly using exogenous filtration markers: 1
- Gold standard methods include plasma or urinary clearance of exogenous markers (iothalamate, iohexol, ⁵¹Cr-EDTA, ⁹⁹mTc-DTPA)
- Use measured GFR when treatment decisions critically depend on precise GFR (kidney donor evaluation, chemotherapy dosing, clinical trials)
- Alternative if measured GFR unavailable: Consider timed urine collections for measured creatinine clearance, though this is less accurate than exogenous marker clearance 1
Clinical Algorithm for GFR Assessment
Follow this stepwise approach: 1
- Start with eGFRcr (creatinine-based estimate) as initial assessment for all patients
- If eGFRcr expected to be inaccurate → Measure cystatin C and calculate eGFRcr-cys
- If eGFRcr-cys still expected to be inaccurate → Measure GFR using exogenous filtration markers
- If measured GFR unavailable and eGFRcr-cys inaccurate → Consider 24-hour urine creatinine clearance
Common Pitfalls to Avoid
- Never rely on serum creatinine concentration alone without calculating eGFR—approximately 60% of patients with abnormal kidney function have normal serum creatinine 4
- Don't assume cystatin C is always superior—it has specific limitations in inflammatory states and with steroid use 1
- Don't ignore clinical context—always consider factors affecting creatinine generation (muscle mass, diet) and cystatin C (inflammation, steroids) when interpreting results 1
- Don't use outdated equations—ensure laboratories use the 2021 race-free CKD-EPI equations with standardized assays 1, 4
Laboratory Standards
Clinical laboratories must implement these standards for accurate cystatin C measurement: 1
- Cystatin C assays must be traceable to international reference standards
- Report cystatin C rounded to nearest 0.01 mg/L
- Report eGFRcys and eGFRcr-cys rounded to nearest whole number in mL/min/1.73 m²
- Flag values <60 mL/min/1.73 m² as "decreased"