Estimating Renal Function for Drug Dosing: Rewriting the Gospel?
One of the hospital pharmacist’s many clinical roles is to estimate renal function, refer to literature references, and adjust medication doses for renal dysfunction. Use of the Cockcroft-Gault (CG) equation for this purpose has long been pharmacists’ “11th commandment”. Recently, however, the increasing availability of estimates of glomerular filtration rate (GFR) from clinical laboratories has led some to call for this commandment to be rewritten. In this paper, we examine this issue and give readers a suggestion for what we think the “new gospel” should entail.
IN THE BEGINNING
The basis for most of today’s renal drug dosing (i.e., dosage adjustments made according to renal function) was described in the 1970s. The relation between renal function and drug clearance was first described by Tozer. Clinicians then required a way to estimate renal function, and Levy was the first to use creatinine clearance to estimate renal function for the purpose of drug dosing. So-called renal drug dosing then proceeded, with creatinine clearance being used to estimate renal function. In 1980 Bennett and others compiled a list of suggested drug dosage adjustments based on the fraction of the drug cleared renally and an estimate of the patient’s renal function. These dosage adjustments are now compiled in a commonly used reference book. The Compendium of Pharmaceuticals and specialties refers to the CG equation, and most product monographs within that resource include recommended dosages for renal dysfunction.
Clinicians need to be aware that using serum creatinine as a marker of renal function has limitations. The renal function of hospitalized patients may change rapidly, and a serum creatinine value at one point in time may not accurately reflect the patient’s present status; rather, it may reflect renal function over the past day or so. Serum creatinine levels can also be affected by muscle wasting, high-protein meals, a vegetarian diet, or fasting. As well, the formula is relatively insensitive for detecting changes in renal function for patients with near-normal serum creatinine. However, this limitation has minimal clinical relevance for the current discussion, as relatively small changes at this level are unlikely to affect drug dosing. Finally, for patients using any type of dialysis, serum creatinine cannot be used as a marker of renal function for drug dosing.
THE “OLD TESTAMENT”
As mentioned above, in 1972, Cockcroft and Gault published a formula to estimate creatinine clearance using the patient’s age, weight, and serum creatinine level; this formula (Equation 1 in Appendix 1) became the “11th commandment” and one of the most commonly used tools in hospital pharmacists’ practice. The equation was developed with data collected from a group of 249 men, 18 to 92 years of age, with stable serum creatinine, factors that potentially limited its generalizability. Because the formula was derived solely from data obtained from men, a 15% adjustment for women was added to correct for the relative difference in the amount of fat and muscle between the sexes; this adjustment was not based on female-derived data. buy antibiotics canada