Calculated Creatinine Clearance
The definition and staging of chronic kidney disease depends on the assessment of glomerular filtration rate (GFR). Inulin clearance is widely regarded as the gold standard for measuring GFR, but requires an intravenous infusion and timed urine collections making it costly and cumbersome. The most widely used measures of GFR in clinical practice are the serum creatinine concentration and the 24-hour creatinine clearance calculation.
The diagnostic usefulness of serum creatinine as an indicator of glomerular filtration rate (GFR) is based upon its constant production from muscle creatine and its relatively constant renal excretion rate. About 1 to 2% of the creatine in muscle is converted to creatinine daily. The amount of creatinine formed is proportional to muscle mass, resulting in differences in serum creatinine concentration related to age, gender and race. Serum creatinine is decreased in individuals with small stature, cachexia, amputations, muscle disease or vegetarian diets. Advanced liver disease causes low serum creatinine because of decreased hepatic conversion of creatine to creatinine.
Serum creatinine is a relatively insensitive indicator of renal disease. A change in serum creatinine from 0.6 -1.2 mg/dL reflects a 50% decline in GFR, even though creatinine is still within the normal range. If a previous baseline creatinine is not available for comparison, a serum creatinine level of 1.2 mg/dL might be considered clinically insignificant.
Calculation of CCr requires collection of a 24-hour urine and a blood sample during the same interval. Twenty four-hour urine collections are considered optimal because they account for diurnal variation in creatinine clearance. The accuracy of the CCr calculation depends on the quality of the 24-hour collection. Errors often occur during collection, transportation or processing. CCr overestimates GFR by 10 to 40% in normal individuals and is even more unpredictable in patients with chronic kidney disease. CCr may not be an accurate estimate of GFR in the following situations:
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Over Estimated |
Under Estimated |
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Cirrhosis |
Body building |
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Muscle wasting |
Anabolic steroids |
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Malnutrition |
Protein & creatine supplements |
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Vegetarian diet |
Congestive heart failure |
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Obesity |
Dehydration |
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Edema |
Trimethoprim, cimetidine |
Because of these limitations, the National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative published the following practice guidelines in February (Am J Kidney Dis 2002; 39:S76-110).
- GFR should be estimated from a prediction equation that takes into account the serum creatinine concentration, age, gender and body size
- Serum creatinine alone should not be used to assess the level of kidney function
- Clinical laboratories should report an estimate of GFR using a prediction equation in addition to reporting serum creatinine
- Measurement of creatinine clearance using a 24-hour urine collection is no more accurate than a GFR prediction equation.
- Creatinine clearance is a better estimate of GFR for patients with exceptional dietary intakes (vegetarian diet or creatine supplements) or muscle mass (amputation, muscle wasting, malnutrition).
The Cockcroft-Gault equation for calculating creatinine clearance is:
Ccr (mL/min) = (140 – age) (weight in kg) (0.85 if female)/72 x serum creatinine
This calculation requires knowledge of the patient’s weight, which is usually not available to laboratories.
The National Kidney Foundation recommended replacing the Cockroft-Gault equation with the Modification of Diet in Renal Disease (MDRD) equation. See Glomerular Filtration Rate Estimation for a more detailed explanation.
