What is the recommended equation for estimating glomerular filtration rate (GFR) in adults using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)?

CKD-EPI Equation for Estimating GFR

Recommended Equation

Use the race-free 2021 CKD-EPI creatinine-based equation (eGFRcr) as the standard initial method for estimating GFR in adults. 1, 2

Primary Approach: Creatinine-Based Estimation

• The 2021 CKD-EPI equation without race is the current recommended standard for adults and should be used as the first-line test for GFR assessment 1, 2
• This equation requires serum creatinine measured by assays calibrated to isotope-dilution mass spectrometry (IDMS) reference methodology 2
• Creatinine values less than 1 mg/dL should be reported to two decimal places (hundredths) for accuracy 2
• The same equation should be used consistently within geographical regions to facilitate communication among providers, patients, and researchers 1

When to Add Cystatin C: The Confirmatory Approach

For patients with eGFRcr 45-59 mL/min/1.73 m² who lack albuminuria or other markers of kidney damage, measure cystatin C and calculate the combined creatinine-cystatin C equation (eGFRcr-cys) to confirm CKD diagnosis. 1, 2

Interpretation Algorithm:

• 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

Performance Data:

• The combined creatinine-cystatin C equation (eGFRcr-cys) demonstrates superior accuracy with only 7.8% of estimates differing by more than 30% from measured GFR in cancer patients, compared to 19.1% for CKD-EPI creatinine alone 3
• The combined equation shows improved agreement across manufacturers with coefficients of variation below 10% and biases below 0.9% 1

Clinical Situations Requiring Alternative Approaches

When eGFRcr is Unreliable:

Consider cystatin C-based or combined equations when patients have: 1, 4, 2

• Extremes of muscle mass (very low or very high) that alter creatinine generation independent of kidney function 4
• Advanced cirrhosis or cancer with high cell turnover where high catabolism and inflammation compromise accuracy 1, 4
• Severe malnutrition or muscle wasting conditions 4
• Obesity class III (BMI >40 kg/m²) 4
• Dietary factors such as high protein or meat intake 4

When Measured GFR is Required:

Use measured GFR with exogenous filtration markers (plasma or urinary clearance) when: 1, 4, 2

• Precise GFR measurement is critical for clinical decision-making 2
• Dosing kidney-cleared chemotherapeutic agents 1, 4
• Even combined eGFRcr-cys may be inaccurate due to radical differences in body composition 1

Common Pitfalls to Avoid

• Do not use the Cockcroft-Gault equation as it is significantly less accurate than CKD-EPI, with 24.9% of estimates differing by more than 30% from measured GFR compared to 19.1% for CKD-EPI 3
• Do not ignore clinical context suggesting altered creatinine generation, such as extremes of muscle mass, dietary intake, or catabolic states 4
• Do not assume eGFRcr accuracy when assessing GFR changes over time without considering potential sources of error 4
• Do not rely on serum creatinine alone without using a validated estimating equation 1, 2

Age-Related Considerations

• CKD-EPI produces higher GFR estimates in younger patients (18-59 years) and lower estimates in elderly patients compared to older equations 5, 6
• The difference between equations diminishes with age, with very little difference in patients over 70 years 6
• In patients aged ≥90 years, CKD-EPI may actually produce lower estimates (mean bias -7.5%) 6