What is Estimated Glomerular Filtration Rate (eGFR)?

What is Estimated Glomerular Filtration Rate (eGFR)?

eGFR is a calculated value derived from serum creatinine (and sometimes cystatin C) combined with demographic variables (age, sex) that serves as the best available index of kidney function for routine clinical practice. 1

Definition and Purpose

• eGFR represents the rate at which the kidneys filter plasma to produce an ultrafiltrate, expressed in mL/min per 1.73 m² of body surface area. 2
• It is used to diagnose chronic kidney disease (CKD), classify disease stages, monitor progression, and calculate appropriate doses of renally-cleared medications. 1
• Normal eGFR is typically >60 mL/min/1.73 m², and values below this threshold indicate potential chronic kidney disease. 3

How eGFR is Calculated and Reported

• Clinical laboratories automatically calculate and report eGFR alongside serum creatinine using validated equations (most commonly the 2021 race-free CKD-EPI equation). 1, 3
• The calculation incorporates serum creatinine from a basic metabolic panel plus age and sex—no additional testing or urine collection is required. 3
• eGFR is reported rounded to the nearest whole number, and values <60 mL/min per 1.73 m² must be flagged as "low" or "decreased." 1
• Laboratory assays must use standardized creatinine measurements with coefficient of variation <2.3% and bias <3.7% compared to reference methodology, preferably enzymatic methods. 1

Advantages Over Direct Measurement

• eGFR is inexpensive, easy to implement, widely available, and easily repeatable compared to measured GFR (mGFR). 1
• Measured GFR requires expensive exogenous filtration markers, multiple blood samples over extended periods, and is only available at specialized centers. 1
• For routine screening and initial assessment, eGFR provides adequate accuracy for most clinical purposes. 4

Critical Limitations and When eGFR is Inaccurate

eGFR is fundamentally "not sufficiently accurate and precise" compared to measured GFR and is subject to multiple non-GFR determinants. 1, 4

Clinical situations where eGFR is unreliable:

• Extremes of muscle mass (very high or very low)—creatinine generation varies with muscle mass independent of kidney function. 1, 4
• Extremes of body size, particularly obesity class III (BMI >40 kg/m²). 1, 4
• Severe malnutrition, muscle wasting diseases, or catabolic states (cancer, cirrhosis, heart failure). 1, 4
• Dietary extremes: low-protein diets, vegetarian diets, keto diets, high-protein diets, or creatine supplements. 1
• Medications affecting creatinine: trimethoprim, cimetidine, anabolic steroids (block tubular secretion). 1, 4
• Rapidly changing kidney function—eGFR lags behind acute changes in GFR. 1

When to Use Alternative Methods

Step 1: Use cystatin C-based eGFR (eGFRcr-cys)

• KDIGO strongly recommends (Grade 1C) using combined creatinine-cystatin C equations when creatinine-based eGFR is expected to be inaccurate and GFR affects clinical decision-making. 1, 4
• Cystatin C is less influenced by muscle mass, diet, age, sex, and race compared to creatinine. 4
• Use eGFRcr-cys for critical drug dosing decisions (especially chemotherapy) or when medications affect creatinine levels. 4

Step 2: Measure GFR directly

• When more accurate GFR ascertainment will impact treatment decisions, measure GFR using plasma or urinary clearance of exogenous filtration markers (iothalamate, iohexol). 1
• Measured GFR is the gold standard, accurate across all GFR ranges, and less influenced by non-GFR determinants. 1
• If mGFR is unavailable and eGFRcr-cys is thought inaccurate, consider 24-hour urine creatinine clearance. 1

Common Pitfalls to Avoid

• Never rely on serum creatinine alone—approximately 60% of patients with abnormal kidney function by eGFR have normal serum creatinine. 4
• Do not ignore clinical context suggesting altered creatinine generation (extremes of muscle mass, dietary intake, catabolic states). 4
• Assess potential for error when evaluating GFR changes over time—eGFR lags behind acute changes and may not reflect rapid deterioration. 1
• Interpretation of serum creatinine requires consideration of dietary protein intake. 1