The creatinine clearance is a widely used test to estimate the glomerular filtration rate (GFR) [1,2]. Creatinine is derived from the metabolism of creatine in skeletal muscle and from dietary meat; it is released into the circulation at a relatively constant rate and has a stable plasma concentration. Like inulin, creatinine is freely filtered across the glomerulus and is neither reabsorbed nor metabolized by the kidney. However, tubular secretion by the organic cation secretory pathways in the proximal tubule accounts for approximately 10 to 20 percent of urinary creatinine in patients with a normal GFR and a progressively higher percentage as the GFR falls [3]. The net effect is progressive overestimation of the GFR with more severe disease.

If the effect of secretion is ignored, then all of the filtered creatinine (equal to the product of the GFR and the serum creatinine concentration [SCr]) will be excreted (equal to product of the urine creatinine concentration [UCr] and the urine flow rate or volume [V]). Thus:

GFR x SCr = UCr x V

GFR = [UCr x V] ÷ SCr

This formula is called the creatinine clearance and tends to exceed the true GFR by 10 to 20 percent or more depending upon the proportion of urinary creatinine that is derived from tubular secretion [4]. Historically, this error was balanced by an error of almost equal magnitude in the measurement of the serum creatinine. The error in serum creatinine measurement was due to non-creatinine chromogens (such as acetone, ascorbic acid, and pyruvate) that are present in serum and contributed 10 to 20 percent of the creatinine concentration measured by older colorimetric techniques. However, national standardization of serum creatinine assays to creatinine reference materials has largely abolished this error. If a laboratory is using standardized methods, creatinine clearance measurements will consistently be 10 to 20 percent higher than GFR in patients with a normal GFR and progressively higher as the GFR falls

Example — Suppose that the following 24-hour urine results are obtained in a 60 kg woman:

SCr = 1.2 mg/dL (106 micromol/L)

UCr = 100 mg/dL (8800 micromol/L)

V = 1.2 L/day

Thus:

CrCl = [100 mg/dL x 1.2 L/day] ÷ 1.2 mg/dL = 100 L/day

To convert this value into units of mL/min, it has to be multiplied by 1000 to convert into mL and then divided by 1440 (the number of minutes in a day):

CrCl = [100 L/day x 1000 ml/L] ÷ 1440 min/day = 70 mL/min

A creatinine clearance calculator is provided (calculator 1), and the results should ideally be normalized to a body surface area (BSA) of 1.73 m2; BSA can be computed using a different calculator.

As an example, a creatinine clearance of 70 mL/min in a small woman with a weight and height of 50 kg and 160 cm, who has a BSA of 1.5 kg/m2, is normalized to a BSA of 1.73 m2 as follows:

CrCl x 1.73/BSA = [70 mL/min x 1.73] ÷ 1.5 = 80 mL/min per 1.73 m2

For a large person with a body surface area of 1.9 kg/m2, the adjusted CrCl would be 64 mL/min per 1.73 m2.

The normal value for the creatinine clearance is 95 ± 20 mL/min per 1.73 m2 in women and 120±25 mL/min per 1.73 m2 in men [2]. Thus, a level of 70 mL/min in a woman suggests the loss of approximately 25 percent of her GFR.

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