College of American Pathologists
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  Which estimate of kidney function is best for drug dosing?


CAP Today




March 2010
Feature Story

For the purpose of drug dosing, which method is better: using the MDRD Study equation to estimate eGFR, or using the Cockcroft-Gault formula to estimate creatinine clearance? What’s important, the NKDEP says, is to consistently use a single kidney function estimate.

A critical study in the development of the NKDEP recommendations (Stevens LA, et al. Comparison of drug dosing recommendations based on measured GFR and kidney function estimating equations. Am J Kid Dis. 2009;54:33–42) looked at the most frequently prescribed drugs that need to have an adjusted dosage, notes Greg Miller, PhD, of Virginia Commonwealth University. The researchers calculated eGFR based on a standardized creatinine value by the MDRD Study equation and by the Cockcroft-Gault formula, the one most frequently used in drug labeling, and compared the differences in dosages that would be made based on those equations. “What they found was that it made little difference which equation you used except in a small number of cases,” Dr. Miller says.

Based on this finding, the NKDEP has taken a practical approach in its recommendations. “The NKDEP says don’t worry about it, use either one, as in most patients, the difference between the estimates is not big, and what we really need is an estimate of kidney function that’s easy for clinicians to do,” says Lesley Stevens, MD, of Tufts Medical Center. “For people with extremes of muscle mass such as extreme muscle wasting or, conversely, people who are extremely healthy—that’s where neither equation is going to be good. But for the vast majority of people, the equations will be in the right ball park, with minimal differences between them.”

The calculation becomes most important for drugs with a narrow therapeutic index (NTI)—the ratio between the therapeutic level and the subtherapeutic or toxic range. So-called NTI drugs are agents for which small changes in systemic concentration can lead to significant changes in the pharmacodynamic response. “With penicillin, for example, you can give a patient twice as much as the dose and it doesn’t make a difference; it’s not a narrow therapeutic index drug. But with other drugs, such as carboplatin, you have got to be careful,” says Andrew Narva, MD, director of the NKDEP.

For most drugs, a comparison of the two methods of estimating shows it doesn’t make a significant difference which is used. “But if there’s a question and someone gets a dramatically different estimate of kidney function based on the Cockcroft-Gault method from one based on MDRD, then they can actually measure kidney function directly, not estimate it.” This technique, formerly useful mainly as a research tool, is increasingly available as a clinical tool at reasonable cost, Dr. Narva says.

—Anne Paxton


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