How is estimated glomerular filtration rate (eGFR) calculated?

How to Calculate Estimated Glomerular Filtration Rate (eGFR)

The most accurate approach for estimating glomerular filtration rate (eGFR) is to use validated equations that incorporate serum creatinine and/or cystatin C, with the 2021 CKD-EPI creatinine-cystatin C equation (without race) being the most accurate for clinical decision-making. 1

Primary eGFR Equations

Creatinine-Based Equations

• The 2021 CKD-EPI creatinine equation (race-free) is currently recommended as the initial test for eGFR assessment in most clinical situations 1
• The Cockcroft-Gault formula is an older equation that estimates creatinine clearance rather than GFR, based on age, gender, body weight, and serum creatinine; it's valid for values >60 ml/min but overestimates kidney function in CKD stages 3-5 1
• The original MDRD (Modification of Diet in Renal Disease) equation has been largely replaced by newer equations due to systematic underestimation of GFR at higher values 2, 3

Cystatin C-Based Equations

• Cystatin C-based equations are recommended when creatinine-based estimates may be inaccurate due to non-GFR determinants of creatinine 1
• Pure cystatin C equations (eGFRcys) can be used in patients with abnormal muscle mass or creatinine generation 1

Combined Creatinine-Cystatin C Equations

• The 2021 CKD-EPI creatinine-cystatin C equation (eGFRcr-cys) provides the most accurate GFR estimates overall 1
• This combined approach is particularly valuable when there are discrepancies between creatinine-based estimates and clinical presentation 1

When to Use Which Equation

Initial Assessment

• Use serum creatinine and an eGFRcr equation for initial assessment of GFR in most patients 1
• Consider potential sources of error in creatinine-based estimates:
  • Factors that affect creatinine generation (muscle mass, diet)
  • Medications that interfere with creatinine secretion
  • Extremes of body size or age 1, 4

When to Add Cystatin C

• Measure cystatin C and use eGFRcr-cys when:
  • eGFRcr is thought to be inaccurate
  • More accurate assessment is needed for clinical decision-making
  • Patient has abnormal muscle mass or nutritional status 1, 5
  • Critical medication dosing decisions are required 1

When to Measure GFR Directly

• Consider direct measurement of GFR using exogenous filtration markers when:
  • Even greater accuracy is required for high-consequence decisions
  • eGFRcr-cys is expected to be inaccurate (e.g., in cases of high inflammation or catabolism)
  • For kidney donor evaluation or chemotherapy dosing 1, 4

Special Considerations

Race and eGFR

• Current guidelines recommend avoiding the use of race in eGFR calculations 1
• The 2021 CKD-EPI equations have eliminated race as a variable while maintaining accuracy 1
• Previous race-based equations could lead to systematic differences in care between racial groups 1

Pediatric Patients

• Use validated pediatric-specific equations for children 1
• Consider enzymatic creatinine assays rather than Jaffe methods in children due to higher relative contribution of non-creatinine chromogens 1

Hospitalized and Malnourished Patients

• Cystatin C-based equations may be more accurate in hospitalized patients with malnutrition or reduced muscle mass 5
• In patients with normal nutritional status, creatinine-based equations perform adequately 5

Clinical Laboratory Considerations

• Laboratories should implement standardized methods for creatinine and cystatin C measurement 1
• Consistent use of the same equation within geographical regions is recommended 1
• Laboratories should consider offering both creatinine and cystatin C measurement capabilities 1

Interpretation of Results

• Normal eGFR values are typically >60 mL/min/1.73 m² 6
• CKD is defined as eGFR <60 mL/min/1.73 m² for ≥3 months 1
• eGFR values should be interpreted in clinical context, not as absolute thresholds 4
• Consider the degree of variability in both eGFR and measured GFR when making clinical decisions 1