Estimating renal function is of great importance for patients taking renally eliminated medications. The glomerular filtration rate (GFR) is an effective indicator of renal function and normal values are approximately 130 mL/min/1.73 m2 for men and 120 mL/min/1.73 m2 for women.1 GFR cannot be directly measured; therefore other measurements must be used to approximate renal function. The gold standard for approximating GFR is the inulin clearance method.2 Inulin is filtered by the glomerulus and is not secreted or reabsorbed, making it an ideal agent for approximating GFR. GFR approximation via inulin clearance is rarely done because it is costly, invasive, and requires a great deal of technical expertise.3 Other markers used to estimate GFR include iothalamate, iohexol, and ethylenediaminetetraacetic acid. Like inulin, these agents are expensive and have limited availability, making them impractical in the clinical setting.
Numerous methods have been developed to estimate GFR. A clinician must balance ease of use and accuracy to determine the best method for estimating GFR in the clinical setting.
Creatinine is an endogenous substance that is eliminated primarily by glomerular filtration and serves an important role in estimating renal function. Creatinine is not as precise as inulin because it undergoes some tubular secretion. The range of serum creatinine (SCr) is approximately 0.6 to 1.2 mg/dL in normal, healthy adults.4 SCr is affected by age, gender, race, diet, muscle mass, and certain drugs; therefore, SCr is not used alone in predicting GFR.2 Muscle mass is a particularly important consideration when analyzing SCr values. Creatinine is a by-product of creatine metabolism and is influenced by the amount of muscle mass present in a patient.2 Patients with low muscle mass would be expected to have lower SCr values. Low muscle mass can occur in elderly, cachectic (eg, acquired immunodeficiency patients), or individuals with limited muscle use (eg, spinal cord injury).
Urinary Clearance of Creatinine
GFR can be estimated via the combination of a timed urine collection and blood sampling of creatinine. The most common time interval utilized is a 24-hour urine collection. This practice has decreased due to the difficulty with accurate collection and data indicating the 24-hour urine collection is equivalent to mathematical equations in estimating GFR.2,5
Creatinine Clearance and GFR Prediction Equations
Equations estimating GFR based on SCr, age, weight, and race are more accurate than SCr alone.2 The Cockcroft-Gault method calculates a creatinine clearance (CrCl) and is a widely used equation to estimate GFR.6
If a patient's actual body weight is below the ideal body weight (IBW), then the actual body weight should be used when calculating CrCl. The Cockcroft-Gault equation may be used for determining drug dosing in obese patients; however, it becomes less accurate in obese patients.
Cockcroft and Gault published this equation in 1976, using data primarily from healthy men. The equation has subsequently been validated in other patient populations. In clinical practice it is customary to round the SCr up to 1.0 mg/dL in patients with actual values <1.0 mg/dL (eg, patients with low muscle mass or age >65).
The Modification of Diet in Renal Disease (MDRD) equation is another calculation utilized to estimate GFR; however, this method is not as common as CrCl.7
The MDRD was originally validated in patients with chronic kidney disease, but was subsequently validated in a large group of patients. MDRD factors race into the equation accounting for increased muscle mass (and therefore SCr) in African American patients.
When dosing medications based on renal function, either Cockcroft-Gault or MDRD are appropriate; however, most pharmacokinetic studies used the Cockcroft-Gault method and the National Kidney Foundation recommends employing Cockcroft-Gault in guiding dosage adjustments.8