Calculating Creatinine Clearance
Use the Cockcroft-Gault formula: CrCl (mL/min) = [(140 - age) × weight (kg)] / [72 × serum creatinine (mg/dL)], multiplied by 0.85 for females. 1, 2
The Cockcroft-Gault Formula
The standard calculation requires four variables 1, 2:
- Age in years
- Weight in kilograms
- Serum creatinine in mg/dL
- Sex (multiply final result by 0.85 for females to account for lower muscle mass) 1
Unit Conversions
Special Population Adjustments
For obese patients, use the mean value between actual body weight and ideal body weight rather than actual weight alone, as recommended by the European Heart Rhythm Association 1, 2. This prevents overestimation since the original formula assumes creatinine clearance increases linearly with body weight 3.
For drug dosing purposes, the American College of Clinical Pharmacy specifically recommends the Cockcroft-Gault equation, particularly for renally-cleared medications with narrow therapeutic windows 1. The American Society of Clinical Oncology echoes this recommendation 1.
Alternative: The MDRD Formula
The abbreviated MDRD study equation provides an alternative that may be more accurate in certain situations 4:
Estimated GFR (mL/min/1.73 m²) = 186 × [serum creatinine (mg/dL)]^-1.154 × [age (years)]^-0.203 × [0.742 if female] × [1.21 if African American] 2
When to Choose MDRD Over Cockcroft-Gault
- MDRD is more accurate when GFR is less than 90 mL/min/1.73 m² 4
- MDRD is superior in patients with significantly impaired renal function (stages 3-5 chronic kidney disease) 4, 2
- MDRD does not require height or weight measurements 4
- MDRD has been validated in kidney transplant recipients and African-Americans with nephrosclerosis 4
When MDRD Should NOT Be Used
The MDRD equation has not been validated and should be avoided in 4:
- Normal persons or GFR >60 mL/min/1.73 m²
- Diabetic kidney disease
- Patients with serious comorbid conditions
- Persons older than 70 years of age
- Extremes of body size (severe malnutrition or obesity)
- Diseases of skeletal muscle, paraplegia, or quadriplegia
- Vegetarian diet
- Rapidly changing kidney function
Critical Pitfalls and Limitations
Laboratory Method Considerations
The Jaffe method overestimates serum creatinine by 5-15% compared to enzymatic methods 1, 2. When using enzymatic (PAP) methods for drug dosing calculations, the National Kidney Foundation recommends adding 0.2 mg/dL to the serum creatinine value to avoid underdosing 1.
Inherent Formula Limitations
- Creatinine clearance overestimates true GFR because creatinine is both filtered and secreted by the kidneys 1, 2
- As renal function declines, tubular secretion and extrarenal elimination of creatinine increase, further exaggerating this discrepancy 2
- The Cockcroft-Gault formula underestimates GFR in normal and moderately reduced renal function but overestimates GFR when renal function is significantly impaired 2
- Both formulas tend to be less accurate in elderly patients 1, 2
When to Measure GFR Directly
Direct measurement using clearance methods (such as urinary clearance of 125I-iothalamate) is necessary in 4:
- Extremes of age and body size
- Severe malnutrition or obesity
- Diseases of skeletal muscle
- Paraplegia or quadriplegia
- Vegetarian diet
- Rapidly changing kidney function
- Calculation of doses for potentially toxic drugs that are renally excreted
Race Considerations
African Americans have higher average muscle mass (32.5% of total body weight versus 28.7% for white subjects), resulting in higher baseline serum creatinine levels 2. The MDRD formula accounts for this with a 1.21 multiplication factor 2.
Do Not Rely on Serum Creatinine Alone
Serum creatinine concentration should never be used as the sole means to assess kidney function 4. Minor elevations in serum creatinine may represent substantial reductions in GFR, particularly in elderly patients, women, and those with lower muscle mass 4.