Variables Used to Calculate eGFR
Estimated glomerular filtration rate (eGFR) is calculated using validated equations that incorporate serum creatinine and/or cystatin C levels, along with age and sex, while race should no longer be included in the calculation 1.
Primary Variables in eGFR Equations
The 2024 KDIGO guidelines recommend using validated equations that incorporate:
- Serum creatinine (SCr) - measured using enzymatic methods when possible, with coefficient of variation <2.3% 1
- Serum cystatin C (SCys) - when measured, requires coefficient of variation <2.0% 1
- Age - incorporated in all validated equations
- Sex - incorporated in all validated equations
- Body surface area (BSA) - results standardized to 1.73 m² 1
Race should be avoided in eGFR computation 1. The 2022 NKF-ASN Task Force explicitly recommended removing race coefficients from equations, as there is no evidentiary basis for keeping race in calculations 2.
Equation Selection
The most commonly recommended approaches are:
- CKD-EPI creatinine equation (CKD-EPIcr) - uses serum creatinine, age, and sex without race
- CKD-EPI creatinine-cystatin C equation (CKD-EPIcr-cys) - combines both markers for improved accuracy 1
- CKD-EPI cystatin C equation (CKD-EPIcys) - uses cystatin C alone when creatinine-based estimates may be unreliable
Reliability of eGFR for Assessing Kidney Function
eGFR is not sufficiently accurate or precise compared to measured GFR (mGFR), but it remains the recommended first-line test for kidney function assessment due to its practicality, despite important limitations 1.
Key Limitations of eGFR
Accuracy Issues
The 2024 KDIGO guidelines explicitly state that eGFR is "not sufficiently accurate and precise" compared to measured GFR 1. Important accuracy limitations include:
- Subject to non-GFR determinant confounding - factors other than actual kidney function affect the results 1
- Lags behind changes in GFR - cannot identify early acute changes in kidney function 1
- Variable performance across GFR ranges - less accurate at higher GFR levels
Non-GFR Determinants That Affect Creatinine
Serum creatinine is influenced by multiple factors unrelated to kidney function 1:
- Muscle mass variations - extremes of body composition (obesity class III, sarcopenia, amputation)
- Dietary factors - high protein intake, vegetarian diets
- Medications - trimethoprim, cimetidine (decrease tubular secretion)
- Catabolic states - tuberculosis, AIDS, hematologic malignancies
- Age-related muscle loss - particularly in elderly populations
Non-GFR Determinants That Affect Cystatin C
While cystatin C is less affected by muscle mass, it has its own confounders:
- Thyroid dysfunction
- Corticosteroid use
- Inflammatory conditions
When eGFR May Be Particularly Unreliable
Consider cystatin C-based eGFR or measured GFR in specific circumstances 1:
- Extremes of body size or muscle mass
- Severe malnutrition or obesity
- Diseases affecting muscle mass
- Paraplegia or quadriplegia
- Vegetarian diet
- When eGFRcr and eGFRcys differ significantly (the direction and magnitude of difference may be informative) 1
Comparative Reliability
The combined creatinine-cystatin C equation (eGFRcr-cys) is more accurate than either marker alone 1, 2. The 2022 NKF-ASN Task Force found that CKD-EPIcr-cys showed:
- Less differential bias between populations
- Increased accuracy in all individuals
- Better decision-making potential for clinical care 2
However, even the combined equation remains less accurate than measured GFR, which is "accurate for GFR in all situations and across the GFR range" but impractical for routine use 1.
Clinical Implications
When to Trust eGFR
eGFR is generally reliable for:
- Screening and initial assessment of kidney function 1
- Monitoring stable chronic kidney disease
- Population-level risk stratification
- Values <60 mL/min/1.73 m² (which should be flagged as low) 1
When to Question eGFR
Assess the potential for error in eGFR when evaluating changes over time 1. Consider measured GFR or alternative testing when:
- Rapid changes in kidney function are suspected
- Precise GFR measurement is needed for critical decisions (living kidney donation, chemotherapy dosing)
- Significant discordance exists between clinical picture and eGFR
- Patient has conditions known to affect creatinine or cystatin C independent of GFR
Laboratory Standards
To maximize reliability, laboratories must 1:
- Use assays traceable to international reference standards
- Maintain desirable bias (<3.7% for creatinine, <3.2% for cystatin C)
- Separate serum from red blood cells within 12 hours
- Report eGFR using validated equations rather than filtration marker concentrations alone
Bottom Line on Reliability
eGFR provides a practical, widely available estimate of kidney function that is adequate for most clinical decisions, but clinicians must recognize it is an imperfect surrogate for true GFR. The combined creatinine-cystatin C equation offers the best balance of accuracy and feasibility when both markers are available 1, 2. For situations requiring precise GFR measurement, measured GFR remains the gold standard despite its practical limitations 1.