How to calculate creatinine clearance?

How to Calculate Creatinine Clearance

Primary Recommendation

Use the Cockcroft-Gault formula for most clinical situations, particularly for drug dosing: CrCl (mL/min) = [(140 - age) × weight (kg)] / [72 × serum creatinine (mg/dL)] × 0.85 if female. 1, 2

Formula Selection by Clinical Context

For Drug Dosing (Most Common Use)

• The Cockcroft-Gault equation is the preferred method for calculating creatinine clearance when adjusting medication doses, especially for renally-cleared drugs with narrow therapeutic windows 2
• The American College of Cardiology, American College of Clinical Pharmacy, and American Society of Clinical Oncology all recommend Cockcroft-Gault for drug dosing purposes 1, 2
• This formula was derived from 249 men aged 18-92 years and assumes a 15% reduction in GFR for females 1

For Assessing Chronic Kidney Disease Stages

• Use the MDRD formula when GFR is less than 90 mL/min/1.73 m²: Estimated GFR = 186 × [serum creatinine (mg/dL)]^-1.154 × [age (years)]^-0.203 × [0.742 if female] × [1.21 if African American] 3, 2
• MDRD is more accurate than Cockcroft-Gault in patients with significantly impaired renal function (stages 3-5 chronic kidney disease) 2
• MDRD provides GFR indexed to body surface area of 1.73 m² 3, 1

For Critically Ill Patients

• Use measured urinary creatinine clearance, NOT estimation formulas 3
• Calculate as: (Urinary creatinine concentration × Urinary volume) / Serum creatinine 3
• Collect urine over at least 1 hour, with urinary creatinine in mmol/L, volume in mL per time unit, and serum creatinine in mmol/L 3
• Estimation formulas (MDRD, CKD-EPI, Cockcroft-Gault) were developed for stable patients with chronic renal insufficiency and must not be used in critically ill patients 3

Body Weight Adjustments

Standard Weight Categories

• Underweight patients: Use actual body weight 4
• Normal weight patients: Use ideal body weight 4
• Overweight, obese, and morbidly obese patients: Use adjusted body weight with a factor of 0.4 (ABW₀.₄), which is the least biased and most accurate method 4
• Alternative for obese patients: Use the mean value between actual body weight and ideal body weight 1, 2

Serum Creatinine Considerations

Low Serum Creatinine Values

• Use the actual serum creatinine value, do not round up 4
• In patients aged 65 years or older with serum creatinine less than 0.8 mg/dL or less than 1 mg/dL, actual serum creatinine is unbiased and more accurate than rounded values 4
• Rounding serum creatinine in patients with low values does not improve accuracy or bias 4

Laboratory Method Adjustments

• The Jaffe method overestimates serum creatinine by 5-15% compared to enzymatic methods 1, 2
• When using enzymatic methods, add 0.2 mg/dL to the serum creatinine value to avoid underdosing medications 2

Unit Conversion

• To convert serum creatinine from μmol/L to mg/dL, divide by 88.4 1

Race-Specific Adjustments

• African Americans have higher baseline serum creatinine due to greater muscle mass (32.5% vs 28.7% of total body weight in white subjects) 1, 2
• The MDRD formula accounts for this with a 1.21 multiplication factor 2
• The Cockcroft-Gault formula does not include a race adjustment 1

Important Limitations and Caveats

When Estimation Formulas Are Unreliable

• Direct measurement using clearance methods is necessary in: extremes of age and body size, severe malnutrition or obesity, diseases of skeletal muscle, paraplegia or quadriplegia, vegetarian diet, rapidly changing kidney function, and calculation of doses for potentially toxic renally-excreted drugs 3, 2

Accuracy Issues by Patient Population

• All formulas are less accurate in elderly patients, particularly those over 70 years 3, 2
• Cockcroft-Gault consistently underestimates GFR in elderly patients, with the discrepancy most pronounced in the oldest patients 1
• The formula is particularly unreliable in extremely elderly women 5
• Cockcroft-Gault underestimates GFR in normal and moderately reduced renal function but overestimates GFR when renal function is significantly impaired 1, 2

MDRD Limitations

• MDRD should be avoided in: normal persons or GFR >60 mL/min/1.73 m², diabetic kidney disease, patients with serious comorbid conditions, persons older than 70 years, extremes of body size, diseases of skeletal muscle, paraplegia or quadriplegia, vegetarian diet, and rapidly changing kidney function 3, 2

Inherent Measurement Issues

• 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, exaggerating the discrepancy between creatinine clearance and actual GFR 1
• Never use serum creatinine concentration alone to assess kidney function 3, 2
• Minor elevations in serum creatinine may represent substantial reductions in GFR, particularly in elderly patients, women, and those with lower muscle mass 2