What is the difference between creatine (Creatinine) clearance and estimated glomerular filtration rate (EGFR) in assessing kidney function?

Creatinine Clearance vs eGFR: Key Differences in Kidney Function Assessment

Use serum creatinine with a validated eGFR equation (not creatinine clearance) as your initial assessment of kidney function in routine clinical practice. 1

What They Measure

eGFR (estimated Glomerular Filtration Rate):

• Calculated from a single blood draw using serum creatinine and demographic variables (age, sex) in validated equations like CKD-EPI 2021 2
• Represents the best available index of kidney function for screening, CKD diagnosis, and staging 2
• Automatically reported by laboratories when serum creatinine is measured, standardized to 1.73 m² body surface area 2
• Does not require urine collection 2

Creatinine Clearance:

• Measured from timed urine collection (typically 24 hours) plus serum creatinine 1
• Represents actual clearance of creatinine from blood, which includes both glomerular filtration AND tubular secretion 1
• Requires accurate, complete urine collection over specified time period 1

Critical Distinction: GFR and Clearance Are Not Synonymous

The KDIGO nomenclature consensus explicitly states that GFR and creatinine clearance are different measurements and should not be used interchangeably. 1 Creatinine clearance typically overestimates true GFR because creatinine undergoes tubular secretion in addition to glomerular filtration 1

When to Use Each Method

Initial Assessment - Use eGFR:

• KDIGO strongly recommends using serum creatinine with an estimating equation for initial GFR assessment (1A recommendation) 1
• More practical, reproducible, and cost-effective than measured clearance 3
• Adequate for most clinical screening and CKD staging purposes 3

When eGFR May Be Inaccurate - Consider Alternatives:

The following conditions compromise eGFR accuracy 1, 3:

• Extremes of muscle mass (very high or very low) 3
• Severe malnutrition or muscle wasting 3
• Class III obesity (BMI >40 kg/m²) 3
• Advanced cirrhosis or high-turnover cancers 1, 3
• Extremes of body size 3
• High protein/meat dietary intake 1, 3

Hierarchical Approach When eGFR Is Unreliable:

1. First-line confirmatory test: Use combined creatinine-cystatin C equation (eGFRcr-cys) when eGFRcr is expected to be inaccurate and GFR affects clinical decisions (1C recommendation) 1

2. Second-line option: Consider measured creatinine clearance with timed urine collection if measured GFR is unavailable AND eGFRcr-cys is thought to be inaccurate 1, 3

3. Gold standard: Measure GFR using plasma or urinary clearance of exogenous filtration markers (e.g., iohexol, iothalamate) when precise GFR is critical for treatment decisions, such as chemotherapy dosing 1, 3

Performance Comparison

Recent evidence demonstrates:

• eGFRcr-cys equations achieve P30 (percentage within 30% of measured GFR) close to 90% and consistently outperform either creatinine-only or cystatin C-only equations 4
• Creatinine clearance from 24-hour urine showed only modest correlation (r: 0.692-0.759) with predictive equations in critically ill patients, with wide variability 5
• In a Swedish cohort of 6,174 patients, all eGFRcr-cys equations had small bias and superior performance compared to eGFRcr alone, even in patients with liver disease, cancer, and heart failure 4

Common Pitfalls to Avoid

With eGFR:

• Ignoring clinical context suggesting altered creatinine generation (muscle mass extremes, dietary factors, catabolic states) 1, 3
• Assuming accuracy when assessing GFR changes over time without considering measurement error 1, 3
• Using eGFR in acute kidney injury when creatinine is rapidly changing—standard equations only work in steady state 6

With Creatinine Clearance:

• Incomplete or inaccurate 24-hour urine collection leads to significant errors 5
• Overestimation of true GFR due to tubular secretion of creatinine 1
• Impractical for routine monitoring due to collection burden 3

Clinical Bottom Line

For routine practice, eGFR from serum creatinine is the standard initial test. 1 When accuracy is critical and eGFRcr is unreliable, escalate to eGFRcr-cys rather than creatinine clearance. 1 Reserve measured creatinine clearance only for situations where measured GFR is unavailable and eGFRcr-cys is thought inaccurate. 1