Are CrCl and GFR the Same?
No, creatinine clearance (CrCl) and glomerular filtration rate (GFR) are not the same—they measure different aspects of kidney function and should never be used interchangeably. 1
Fundamental Differences
GFR represents the true rate at which kidneys filter blood through the glomeruli, ideally measured using exogenous markers like inulin, iohexol, or 51Cr-EDTA that are purely filtered without any tubular handling. 2 This is the gold standard measure of kidney function. 1
Creatinine clearance measures how quickly creatinine is removed from the blood, but creatinine is both filtered by the glomerulus AND secreted by the renal tubules. 2 This tubular secretion causes CrCl to systematically overestimate true GFR, particularly as renal function declines. 1, 2
Why This Distinction Matters Clinically
The key issue is that as renal function declines, tubular secretion and extrarenal elimination of creatinine increase, exaggerating the discrepancy between creatinine clearance and actual GFR. 2 At GFR levels between 20-40 mL/min/1.73 m², the fractional excretion of creatinine averages 1.21, meaning CrCl overestimates true GFR by approximately 21%. 3
Different Clinical Applications
For diagnosing and staging chronic kidney disease: Use estimated GFR (eGFR) from equations like MDRD or CKD-EPI, which provide GFR indexed to body surface area (mL/min/1.73 m²). 1, 2
For medication dosing decisions: Use the Cockcroft-Gault equation to estimate creatinine clearance, as drug manufacturers and pharmacokinetic studies historically used this formula to establish renal dosing guidelines. 2, 4
Measurement and Estimation Methods
Measured GFR using exogenous filtration markers (clearance methods with iohexol, inulin, or 51Cr-EDTA) should be noted separately from estimated values. 1 These provide the most accurate assessment when formulas are unreliable, particularly in patients with extremes of body composition. 2
Estimated GFR equations (CKD-EPI, MDRD) use serum creatinine, age, sex, and race to estimate GFR normalized to 1.73 m² body surface area. 1 These are designed for CKD diagnosis and staging, not medication dosing. 2
Estimated creatinine clearance using the Cockcroft-Gault formula provides an unnormalized estimate in mL/min that accounts for body weight, making it more appropriate for drug dosing. 2, 4
Common Pitfalls to Avoid
Never use serum creatinine alone to assess kidney function, especially in elderly patients where muscle mass loss decreases creatinine production independently of kidney function. 1, 2, 5 A serum creatinine of 1.2 mg/dL can represent a creatinine clearance of 110 mL/min in a young adult but only 40 mL/min in an elderly patient. 2, 5
Do not use normalized eGFR (mL/min/1.73 m²) for medication dosing, as this leads to underdosing in larger patients and overdosing in smaller patients. 2 Drug package inserts reference Cockcroft-Gault-derived creatinine clearance values. 2
24-hour urine collections for measured CrCl are prone to significant collection errors and offer no increased precision over calculated estimates in predicting GFR. 3, 4
Accuracy Considerations
The Cockcroft-Gault formula consistently underestimates GFR in patients with normal to moderately reduced renal function, but overestimates GFR in patients with significantly impaired renal function (CrCl <30 mL/min) due to increased tubular secretion at low GFR levels. 2, 6 This formula is particularly inaccurate in elderly patients, with the discrepancy most pronounced in the oldest patients. 2, 6
The MDRD and CKD-EPI equations show tighter correlation with measured GFR than 24-hour creatinine clearance and are more accurate for CKD staging. 1, 7 However, they should not replace Cockcroft-Gault for medication dosing decisions. 4