Recommended Equation for Computing eGFR
Use the 2021 CKD-EPI creatinine equation (race-free) as the standard method for estimating GFR in adults with impaired renal function. 1, 2
Primary Recommendation: CKD-EPI 2021 Equation
The CKD-EPI equation has replaced the MDRD equation as the preferred method for eGFR calculation because it demonstrates superior performance, particularly at GFR levels above 60 mL/min/1.73 m². 3, 1, 2 This equation requires only:
- Standardized serum creatinine (calibrated to IDMS)
- Patient age
- Patient sex
- No race variable (as of the 2021 update) 2
The CKD-EPI equation shows less bias than MDRD (-8 vs -11 mL/min/1.73 m²), improved precision, and greater accuracy (84.1% vs 80.6% of estimates within 30% of measured GFR). 4, 5 It performs better across the entire GFR spectrum and provides more accurate cardiovascular risk stratification in patients with chronic kidney disease. 6
Alternative Equations for Specific Clinical Scenarios
When CKD-EPI May Be Inadequate
Add cystatin C measurement and use the combined CKD-EPI creatinine-cystatin C equation when: 2
- Extremes of muscle mass are present
- Advanced cirrhosis exists
- Active malignancy is present
- eGFR is 45-59 mL/min/1.73 m² without other markers of kidney damage 3, 2
- Severe malnutrition or cachexia affects muscle mass 7
Cystatin C-based equations show the lowest bias (-3 mL/min/1.73 m²) and best precision in heart failure patients and those with altered nutritional status. 4, 7
Historical Equations (Now Superseded)
MDRD equation: More accurate than Cockcroft-Gault for GFR <90 mL/min/1.73 m² but systematically underestimates at higher GFR values and has been replaced by CKD-EPI. 3, 2
Cockcroft-Gault equation: Overestimates kidney function in CKD stages 3-5, requires body weight, and shows worse precision than CKD-EPI despite lower bias in some populations. 3, 2, 4
Critical Implementation Requirements
Laboratory Standards
Serum creatinine assays must be: 3, 2
- Calibrated to isotope-dilution mass spectrometry (IDMS) reference standards
- Reported to two decimal places when values are <1 mg/dL
- Never used alone to assess kidney function 3
Clinical laboratories should automatically report eGFR using the CKD-EPI 2021 equation whenever serum creatinine is ordered. 1, 2
When to Measure GFR Directly
Consider measured GFR using exogenous markers (iohexol or iothalamate clearance) when: 3, 2
- Extremes of age or body size exist
- Calculating doses of potentially toxic drugs excreted by kidneys
- Rapidly changing kidney function is present
- Paraplegia or quadriplegia affects muscle mass
- Vegetarian diet significantly reduces creatinine generation
- Precise GFR measurement is critical for major clinical decisions (e.g., kidney donation evaluation) 2
Special Populations
For children (<18 years): Use pediatric-specific equations such as the Schwartz formula or Full Age Spectrum (FAS) equation, not adult equations. 3, 2
For patients with glomerular disease: No eGFR equation has been specifically validated; consider measured GFR for critical decisions as hypoalbuminemia, glucocorticoids, and low muscle mass significantly affect estimates. 2
Common Pitfalls to Avoid
- Do not use serum creatinine alone as it fails to detect GFR decline until kidney function drops to approximately 50% of normal. 3
- Do not use race-based adjustments in the 2021 CKD-EPI equation. 1, 2
- Do not apply adult equations to children as they systematically misestimate GFR in pediatric populations. 3, 2
- Do not rely on creatinine-based equations in hospitalized patients with malnutrition without considering cystatin C-based alternatives. 7