Relationship Between Creatinine Clearance and eGFR
Creatinine clearance and eGFR are both methods to assess kidney function, but eGFR calculated from serum creatinine using validated equations (such as CKD-EPI) is the preferred initial test for routine clinical practice, while creatinine clearance from timed urine collections is generally less accurate and more cumbersome. 1, 2
Key Conceptual Differences
Creatinine clearance measures the volume of blood plasma cleared of creatinine per unit time, requiring both a timed urine collection (typically 24-hour) and a serum creatinine measurement. 2
eGFR is calculated using validated equations that incorporate serum creatinine and/or cystatin C along with demographic variables (age, sex, race), without requiring any urine collection. 1, 2
Both methods attempt to estimate the same underlying parameter—glomerular filtration rate—but use fundamentally different approaches. 2
Clinical Performance and Accuracy
Why eGFR is Preferred
eGFR provides comparable or superior accuracy to creatinine clearance while being far more convenient, as demonstrated in the MDRD study where predicted GFR was more accurate than measured creatinine clearance when compared to gold-standard iothalamate clearance. 1
Clinical laboratories should automatically report eGFR alongside serum creatinine concentrations, rounded to the nearest whole number in mL/min/1.73 m², with values <60 mL/min/1.73 m² flagged as decreased. 1, 3
Measurement of creatinine clearance by timed urine collections does not provide more accurate estimates of GFR than prediction equations. 1
Limitations of Creatinine Clearance
24-hour urine collections are inconvenient and frequently inaccurate due to incomplete collection, with studies showing 42.6% of collections deemed inaccurate when rigorously assessed. 4
Creatinine clearance systematically overestimates true GFR because creatinine undergoes tubular secretion in addition to glomerular filtration, with the degree of overestimation increasing as GFR declines (potentially approaching twice the true GFR at levels of 15-20 mL/min). 1
The fractional excretion of creatinine increases with decreasing GFR, meaning the overestimation becomes more pronounced in advanced kidney disease. 5
Limitations of eGFR
eGFR may be less accurate in patients with extremes of muscle mass (very high or very low), very elderly patients, extremes of body size, or those with unusual dietary intake, because creatinine generation varies with muscle mass in ways not fully captured by estimating equations. 1, 2, 3
eGFR has not been specifically validated for glomerular diseases and/or nephrotic syndrome, where hypoalbuminemia may lead to overestimation of true GFR due to increased tubular creatinine secretion. 1
Glucocorticoids may increase serum cystatin C, potentially underestimating eGFR when cystatin C-based equations are used. 1
All estimates are valid only in steady-state; acute kidney injury confounds all GFR estimates. 1
When to Use Each Method
Use eGFR as First-Line
For routine kidney function assessment, CKD staging, screening, and most clinical decision-making, eGFR based on serum creatinine (using CKD-EPI equation) should be the initial test. 1, 2, 3
The CKD-EPI equation performs better than older equations (MDRD), with less bias, improved precision, and greater accuracy, especially at higher GFR levels. 6
Consider Creatinine Clearance
When eGFR is thought to be inaccurate due to extremes of muscle mass or dietary intake, and measured GFR using exogenous markers is not available. 1, 2
In living kidney donor evaluation, the average of creatinine clearance and eGFR provides better accuracy than either measure alone, essentially eliminating bias (though this does not hold true for Black patients where all measures may overestimate GFR). 4
Use Measured GFR with Exogenous Markers
When more accurate ascertainment of GFR will impact treatment decisions, such as determining eligibility for preemptive kidney transplant, adjusting chemotherapy doses, or evaluating living kidney donors. 1, 7
Gold standard methods include inulin clearance, radioisotopic plasma clearance, or non-radioisotopic markers like iohexol. 1, 7
Critical Technical Considerations
Standardization Requirements
Creatinine assays must be calibrated to isotope-dilution mass spectrometry standards with coefficient of variation <2.3% and bias <3.7%, preferably using enzymatic methods rather than Jaffe methods. 1, 3, 8
Failure to standardize creatinine assays can cause errors in GFR estimates as high as 20%, particularly problematic in patients with near-normal serum creatinine. 1
Different creatinine assay methods (e.g., CX3 vs. Hitachi) can produce significantly different results, with some methods overestimating serum creatinine and thus underestimating GFR. 5
Common Pitfalls to Avoid
Do not rely on serum creatinine alone to assess kidney function, as it does not rise above normal until GFR falls to approximately half the normal level, and age-related decline in muscle mass masks declining GFR in elderly patients. 1
Do not routinely obtain 24-hour urine collections for GFR assessment when eGFR is available and appropriate. 1, 2
Do not assume creatinine clearance is more accurate than eGFR—despite requiring substantially more time and effort, timed creatinine clearance offers no increased precision over equations based on serum creatinine, age, sex, and weight. 5
When creatinine clearance is needed, consider using the average of creatinine and urea clearances at low GFR levels (15-20 mL/min) to obtain a more valid approximation, as creatinine clearance alone may overestimate GFR by nearly twofold at these levels. 1