Sensitivity of eGFR for Detecting Chronic Kidney Disease
eGFR has poor sensitivity for detecting early CKD (Stage 1-2) but excellent sensitivity for detecting Stage 3-5 CKD (eGFR <60 mL/min/1.73 m²), though it systematically misses approximately 16-20% of individuals with true kidney dysfunction when creatinine-based equations are used alone. 1
Understanding the Fundamental Limitation
The critical issue is that eGFR >60 mL/min/1.73 m² does not exclude kidney disease. 2 This is because:
- The reference interval for healthy adults using MDRD equations ranges from 63.5-124.6 mL/min/1.73 m², which overlaps substantially with CKD Stage 1 and 2 values 2
- Up to 25% of people with normal serum creatinine (particularly thin, elderly women) have significantly reduced eGFR (<60 mL/min/1.73 m²) that goes undetected 3
- Serum creatinine alone is an unreliable marker because it varies with age, sex, muscle mass, and diet, with interlaboratory variation as high as 20% 3
Sensitivity by CKD Stage
Stage 3-5 CKD (eGFR <60 mL/min/1.73 m²)
- High sensitivity: eGFR reliably detects moderate to severe kidney dysfunction 1
- Laboratories are instructed to flag all eGFR values <60 mL/min/1.73 m² as abnormally low 1
- This threshold represents loss of half or more of normal adult kidney function 4
Stage 1-2 CKD (eGFR ≥60 mL/min/1.73 m²)
- Poor sensitivity: eGFR cannot detect early kidney damage without additional markers 5, 2
- CKD diagnosis at these stages requires persistent albuminuria (UACR ≥30 mg/g), glomerular hematuria, pathological abnormalities on biopsy, or radiographic abnormalities 5
- Patients with normalized eGFR but persistent albuminuria remain at elevated cardiovascular and mortality risk 5
Accuracy Limitations of Creatinine-Based eGFR
Creatinine-based eGFR is inaccurate in 16-20% of individuals with eGFR <60 mL/min/1.73 m² when compared to measured GFR. 1 This occurs due to:
- Non-GFR determinants including creatinine secretion, generation from muscle mass, and extrarenal excretion 1, 4
- Systematic underestimation at higher GFR values 4
- Lack of validation in extremes of muscle mass, obesity, amputees, diabetic kidney disease, severe comorbidities, and those >70 years 4
Improving Sensitivity: When to Use Confirmatory Testing
When creatinine-based eGFR appears discordant with clinical picture, measure cystatin C-based eGFR or consider measured GFR. 1, 6 Specific scenarios include:
- Extremes of muscle mass (bodybuilders, cachexia, amputees) 1, 4
- Vegetarian diet or recent changes in meat intake 4
- eGFR 45-59 mL/min/1.73 m² without albuminuria or other kidney damage markers 6
- Uncertainty about CKD diagnosis or progression 1
The combined creatinine-cystatin C equation (eGFRcr-cys) provides superior accuracy compared to either marker alone, particularly at GFR values >60 mL/min/1.73 m². 1, 4
Critical Clinical Pitfall
Never use serum creatinine alone to assess kidney function. 4, 6 Factors such as recent exercise, infection, fever, marked hyperglycemia, or hypertension can elevate creatinine independently of kidney damage. 4 Always calculate eGFR using validated equations and assess for albuminuria to avoid missing early CKD. 1, 5
Laboratory Reporting Standards to Maximize Detection
To optimize sensitivity, laboratories should:
- Report eGFR automatically with every serum creatinine measurement 1, 3
- Use enzymatic methods for creatinine assay (coefficient of variation <2.3%) rather than Jaffé method 1, 4
- Report eGFR values >60 mL/min/1.73 m² as ">60 mL/min/1.73 m²" rather than precise figures, since accuracy is suboptimal at normal/near-normal function 3
- Flag all values <60 mL/min/1.73 m² as low 1
- Measure both creatinine and cystatin C on the same sample when cystatin C is ordered 1