What is the best method to calculate estimated Glomerular Filtration Rate (eGFR)?

How to Calculate eGFR

Use the 2021 CKD-EPI creatinine equation (without race) as your first-line method for calculating eGFR in adults, with serum creatinine measured by an IDMS-traceable assay. 1, 2

Initial Assessment Approach

For routine clinical evaluation in adults, calculate eGFR using serum creatinine with a validated estimating equation rather than relying on creatinine values alone. 1 The 2021 CKD-EPI creatinine equation (eGFRcr) has replaced older formulas as the recommended standard because it provides superior accuracy, particularly at GFR levels above 60 mL/min/1.73 m². 1, 2, 3

Laboratory Requirements for Accurate Calculation

Your laboratory must meet specific technical standards for the creatinine measurement to be valid:

• Creatinine assays must be calibrated to isotope-dilution mass spectrometry (IDMS) reference methodology 1, 2
• Values below 1 mg/dL should be reported to two decimal places (hundredths) 2
• The laboratory should automatically report eGFR alongside the creatinine value 1, 2
• Results should be rounded to the nearest whole number and expressed as mL/min/1.73 m² 1

When to Add Cystatin C for Confirmation

Add cystatin C measurement to calculate the combined creatinine-cystatin C equation (eGFRcr-cys) when eGFRcr is 45-59 mL/min/1.73 m² without other markers of kidney damage (such as proteinuria). 1, 2 This confirmatory approach is particularly important because:

• If eGFRcr-cys is also <60 mL/min/1.73 m², CKD is confirmed 1
• If eGFRcr-cys is ≥60 mL/min/1.73 m², CKD is not confirmed 1
• The combined equation provides superior accuracy compared to creatinine alone 1, 4

Clinical Situations Requiring Alternative Approaches

Consider using cystatin C-based equations or measured GFR in specific circumstances where creatinine-based estimates are unreliable:

Extremes of Body Composition

• Severe obesity or cachexia - creatinine production varies significantly with muscle mass 1, 2
• Amputees - reduced muscle mass leads to overestimation of GFR 1
• Elderly patients with sarcopenia - low muscle mass causes falsely elevated eGFR 5

Medical Conditions Affecting Creatinine

• Advanced cirrhosis - altered creatinine metabolism and muscle wasting 1, 2
• High cell turnover cancers - increased catabolism affects both creatinine and cystatin C 1
• Dietary factors - high protein intake or creatine supplementation 2

When Precision is Critical

Use measured GFR (mGFR) with exogenous filtration markers (iohexol, iothalamate, or inulin) when precise GFR measurement is essential for clinical decision-making, such as dosing nephrotoxic chemotherapy agents with narrow therapeutic windows. 1, 2 While mGFR is the gold standard, it is expensive, labor-intensive, and impractical for routine monitoring. 1

Practical Implementation Algorithm

1. Start with eGFRcr using the 2021 CKD-EPI equation for all adults 1, 2

2. If eGFRcr is 45-59 mL/min/1.73 m² AND no proteinuria is present:

   • Add cystatin C measurement 1
   • Calculate eGFRcr-cys 1, 2
   • Use this combined value to confirm or exclude CKD 1

3. If extremes of muscle mass, body composition, or specific medical conditions exist:

   • Consider cystatin C-based equations as first-line 1, 2
   • The 2012 CKD-EPI cystatin C equation does not require race specification 4

4. If critical precision is needed (e.g., chemotherapy dosing):

   • Obtain measured GFR with exogenous markers 1, 2

Common Pitfalls to Avoid

Do not use the MDRD equation for routine clinical practice - it systematically underestimates GFR at higher levels and has been superseded by CKD-EPI equations. 1, 6, 3 The CKD-EPI equation reclassifies approximately 23% of patients to more accurate risk categories compared to MDRD. 6

Do not adjust eGFR for body surface area when dosing medications - most eGFR equations report values normalized to 1.73 m². For drug dosing, you may need to back-calculate to absolute clearance (mL/min) by multiplying by the patient's actual body surface area divided by 1.73. 1

Avoid relying solely on serum creatinine concentration - a "normal" creatinine can mask significant kidney dysfunction, especially in elderly patients or those with reduced muscle mass. 1, 5

Equation Comparison and Performance

The CKD-EPI creatinine equation demonstrates superior performance compared to older formulas:

• Better accuracy at GFR >60 mL/min/1.73 m² - 84% of estimates fall within 30% of measured GFR versus 81% for MDRD 3
• Less bias - median difference of 2.5 mL/min/1.73 m² versus 5.5 for MDRD 3
• Improved risk stratification - net reclassification improvement of 8.7% for cardiovascular outcomes 7
• Lower CKD prevalence estimates - reduces overdiagnosis at borderline GFR levels 6, 3

The combined creatinine-cystatin C equation (eGFRcr-cys) provides the highest accuracy overall, with 86% of estimates within 30% of measured GFR. 4, 5