GFR and Creatinine Clearance Are Not the Same
No, GFR (glomerular filtration rate) and CrCl (creatinine clearance) are not the same, though they are related measures of kidney function that are often used interchangeably in clinical practice despite important differences. 1
Key Differences Between GFR and CrCl
What They Actually Measure
GFR represents the true rate at which the kidneys filter blood through the glomeruli, ideally measured using exogenous markers like inulin, 51Cr-EDTA, or iohexol that are purely filtered without tubular secretion or reabsorption 1, 2
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, causing CrCl to overestimate true GFR 1, 3
The Magnitude of Discrepancy
As renal function declines, tubular secretion of creatinine increases proportionally, causing the gap between CrCl and true GFR to widen 1, 4
In patients with GFR between 20-40 mL/min/1.73 m², the fractional excretion of creatinine averages 1.21, meaning CrCl overestimates GFR by approximately 21% 3
CrCl provides only a crude measure of renal function and consistently overestimates true GFR because creatinine undergoes both filtration and tubular secretion 1, 4
Clinical Implications for Practice
When to Use Each Measure
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, 4
For medication dosing decisions: Use the Cockcroft-Gault equation to estimate creatinine clearance, as this is what pharmaceutical companies historically used to establish renal dosing guidelines for most medications 4, 5
Critical Pitfall to Avoid
Never use serum creatinine alone to assess kidney function, as it significantly underestimates renal insufficiency, particularly in elderly patients where muscle mass is reduced 1, 6
In cancer patients with normal serum creatinine, one in five had asymptomatic renal insufficiency when assessed by CrCl methods 1
A serum creatinine of 1.2 mg/dL could represent a CrCl of 110 mL/min in a 30-year-old 90 kg male athlete but only 40 mL/min in a 75-year-old 65 kg woman 1
Estimation Methods and Their Accuracy
Cockcroft-Gault Formula
Consistently underestimates GFR in patients with normal to moderately reduced renal function 1, 6
Overestimates GFR in patients with significantly impaired renal function due to increased tubular secretion at low GFR levels 1
Despite these limitations, remains the standard for medication dosing because drug manufacturers used this formula to establish dosing recommendations 4, 5
MDRD and CKD-EPI Equations
Provide GFR estimates indexed to body surface area (mL/min/1.73 m²), designed for diagnosing and staging chronic kidney disease 4
More accurate than Cockcroft-Gault in patients with significantly impaired renal function 6, 4
Should not be used for medication dosing as they can lead to underdosing in larger patients and overdosing in smaller patients 4
24-Hour Urine Collection for CrCl
Prone to inaccuracy due to incomplete urine collection 1
In critically ill patients with acute kidney injury, urinary CrCl showed a within-group error of 55% compared to 7.2% for measured GFR using 51Cr-EDTA 7
Despite requiring substantially more effort, 24-hour CrCl offers no increased precision over Cockcroft-Gault calculation in predicting GFR 3
Practical Algorithm for Clinical Use
Initial screening: Calculate eGFR using serum creatinine-based equations (MDRD or CKD-EPI) for all patients 1
Confirm kidney function when precise assessment is needed (pre-nephrectomy, chemotherapy dosing) using measured GFR with exogenous markers or measured creatinine clearance 1
For medication dosing: Use Cockcroft-Gault equation, particularly for drugs with narrow therapeutic indices 4
In elderly or low-weight patients: Use Cockcroft-Gault with ideal body weight rather than actual body weight to avoid overestimating renal function 6
Never rely on serum creatinine alone, even when values appear normal, as this commonly misses renal insufficiency 1, 6