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FOUNDATION OVERVIEW

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Estimating renal function is important for patients taking renally eliminated medications in order to maximize effectiveness while limiting toxicity. 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. The gold standard for approximating GFR is the inulin clearance method. Inulin is filtered by the glomerulus and is not secreted or reabsorbed, making it an ideal agent for approximating GFR. The inulin clearance method is rarely done because it is costly, invasive, and requires technical expertise. Additional markers used to estimate GFR include iothalamate, iohexol, and ethylenediaminetetraacetic acid. Like inulin, these markers are expensive and have limited availability, making them impractical in the clinical setting. Numerous methods have been developed to estimate GFR and examples include the Cockcroft-Gault and the Modification of Diet in Renal Disease (MDRD) equations.

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Serum Creatinine

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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. SCr is affected by age, gender, race, diet, muscle mass, and certain drugs; therefore, SCr is not used alone in predicting GFR. Muscle mass is an important consideration when analyzing SCr values. Creatinine is a by-product of creatine metabolism and is influenced by the amount of muscle mass in a patient. Patients with low muscle mass would be expected to have lower SCr values. Low muscle mass can occur in elderly, cachectic patients (eg, acquired immunodeficiency patients), or individuals with limited muscle use (eg, spinal cord injury). Therefore, low muscle mass patients may have SCr values in the normal range but actually have renal insufficiency.

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Urinary Clearance of Creatinine

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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.

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Creatinine Clearance and GFR Prediction Equations

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Equations estimating GFR based on SCr, age, weight, and race are more accurate than SCr alone. The Cockcroft-Gault method calculates a creatinine clearance (CrCl) and is a widely used equation to estimate GFR.

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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. It is important to understand the manufacturer’s recommendation for an individual medication as actual body weight has been used by some when giving dosage recommendations based on the Cockcroft-Gault equation. Therefore, an overestimation of renal ...

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