Am Fam Physician. 2007 Nov 15;76(10):1454-1455.
to the editor: We read with interest the article on chronic kidney disease (CKD) in American Family Physician.1 The authors state that using the Modification of Diet in Renal Disease (MDRD) study equation “has been shown to be the best method for detecting a GFR [glomerular filtration rate] lower than 90 mL per minute per 1.73 m2 in older patients.”1 This statement is well founded; however, the MDRD equation has not been validated for use in drug dosing.
Current clinical practice guidelines from the National Kidney Foundation Kidney Disease Outcomes Quality Initiative indicate that either the MDRD or Cockcroft-Gault (CG) equations may be used in the estimation of GFR. The guidelines state that estimation of GFR allows proper dosing of drugs excreted by glomerular filtration. The guidelines indicate that the CG equation was developed for estimating creatinine clearance, whereas the MDRD equation may perform better at the estimation of GFR.2 This leaves significant confusion about which equation should be used for drug dosing adjustments. Other sources make the answer evident. The U.S. Food and Drug Administration recommends that package insert dosing recommendations be made based on the CG equation.3 As a result, this equation is widely used in pharmacokinetic studies and in the determination of drug dosing adjustments by manufacturers. The National Kidney Disease Education Program (NKDEP) recognized this discrepancy and released recommendations regarding the recalibration of serum creatinine assays in July 2006. The authors state: “For drug dosing purposes, NKDEP does not recommend using the MDRD Study equation at this time because the clinical impact on drug dose adjustment has not been compared between current practice and the MDRD Study equation.”4 Therefore, it makes little difference to determine populations in which the MDRD equation may better approximate true GFR, because dosing for most drugs has been determined by the CG equation.
Using the MDRD equation for drug dosing may have important clinical implications. A retrospective analysis demonstrated that as many as 37 percent of patients would be dosed differently if the MDRD equation was used to estimate creatinine clearance compared with the CG equation.5
Although the CG equation is not the most accurate representation of GFR in some patients, it should be considered the standard for estimating creatinine clearance for the purpose of drug dosing. However, MDRD results should be incorporated into the clinical decision-making process. As the NKDEP states: “the MDRD Study equation is an important tool for identifying patients at risk for CKD…Utilizing the MDRD Study equation to identify patients at risk for CKD provides pharmacists an opportunity to collaborate with physicians in optimizing medical management of these patients.”4
Author disclosure: Nothing to disclose.
1. Munar MY, Singh H. Drug dosing adjustments in patients with chronic kidney disease. Am Fam Physician. 2007;75:1487–96.
2. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39(2 suppl 1):S1–266.
3. Center for Drug Evaluation and Research. Guidance for industry pharmacokinetics in patients with impaired hepatic function: study design, data analysis, and impact on dosing and labeling. Accessed May 31, 2007, at: http://www.fda.gov/cder/guidance/index.htm.
4. NKDEP. Recommendations for pharmacists and authorized drug prescribers. Accessed May 31, 2007, at: http://nkdep.nih.gov/labprofessionals/Pharm_Recommendations_508.pdf.
5. Wargo KA, Eiland EH III, Hamm W, English TM, Phillippe HM. Comparison of the modification of diet in renal disease and Cockcroft-Gault equations for antimicrobial dosage adjustments. Ann Pharmacother. 2006;40:1248–53.
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