In Reply to ‘Estimated GFR for Drug Dosing: A Bedside Formula’, ‘Drug Dose Adjustments in Patients With Renal Impairment’, ‘Use of the MDRD Study Equation for Drug Dosing’, and ‘Estimated GFR vs Creatinine Clearance for Drug Dosing’

Abstract

We agree with Dr Jones1Jones G.R.D. Estimated GFR for drug dosing: a bedside formula.Am J Kidney Dis. 2009; 54: 982-983Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar and Czock and colleagues2Czock D. Bertsche T. Haefeli W.E. Drug dose adjustments in patients with renal impairment.Am J Kidney Dis. 2009; 54: 983-984Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar that adjustment of the Modification of Diet in Renal Disease (MDRD) Study equation for body surface area (BSA) is essential in patient demographic extremes and when dosing drugs with a narrow therapeutic index. We thank Dr Jones for his suggested approach. We agree with Drs Saad and Cassagnol3Saad M. Cassagnol M. Use of the MDRD Study equation for drug dosing.Am J Kidney Dis. 2009; 54: 984Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar on the importance of clinical outcomes in the evaluation of the appropriateness of drug doses. However, we disagree with their conclusion, shared by Dowling et al, that use of the Cockcroft-Gault equation is preferred for drug dosing. The rationale for using the Cockcroft-Gault equation in the 1998 US Food and Drug Administration (FDA) guidance was that it was the most practical means to estimate glomerular filtration rate at that time. The lesser accuracy and greater imprecision of the Cockcroft-Gault equation than the MDRD Study equation when compared to a reference standard4Stevens L.A. Coresh J. Greene T. Levey A.S. Assessing kidney function–measured and estimated glomerular filtration rate.N Engl J Med. 2006; 354: 2473-2483Crossref PubMed Scopus (2306) Google Scholar, 5Stevens L.A. Manzi J. Levey A.S. et al.Impact of creatinine calibration on performance of GFR estimating equations in a pooled individual patient database.Am J Kidney Dis. 2007; 50: 21-35Abstract Full Text Full Text PDF PubMed Scopus (180) Google Scholar would suggest that dosing adjustments based on the Cockcroft-Gault equation are less likely to be correct. Studies that do not include comparison to a reference method, as was used in our study, are not able to draw conclusions as to which equation provided the better dosage estimate. In addition, most of the literature comparing the 2 equations for drug dosages is methodologically flawed; most do not use standardized creatinine or rely on different metrics for comparison. More importantly, Saad and Cassagnol3Saad M. Cassagnol M. Use of the MDRD Study equation for drug dosing.Am J Kidney Dis. 2009; 54: 984Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar and Dowling et al6Dowling T.C. Matzke G.R. Murphy J.E. Estimated GFR vs creatinine clearance for drug dosing.Am J Kidney Dis. 2009; 54: 984-985Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar do not account for the effect of variation in creatinine assays. Pharmacokinetic studies performed and corresponding dosing recommendations formulated prior to the availability of standardized creatinine methods were dependent on the particular creatinine method used in a given study. As a result, recommended drug dosages have been inconsistently translated into clinical practice. It is time to move beyond the focus on differences among equations and towards a focus on using the most accurate clinical data to improve the care of our patients.7Stevens LA, Levey AS. Use of MDRD Study equation to estimate kidney function for drug dosing. Clin Pharmacol Ther, in press.Google Scholar, 8National Kidney Disease Education ProgramEstimation of kidney function for prescription medication dosage in adults.http://www.nkdep.nih.gov/professionals/drug-dosing-information.htmGoogle Scholar Going forward, pharmacokinetic studies should be performed with standardized creatinine values and the most accurate equations. For drugs already approved, it is impractical to suggest that all prior studies be repeated and our results show reasonable similarities in assigned drug dosages using either equation. Financial Disclosure: None. Estimated GFR vs Creatinine Clearance for Drug DosingAmerican Journal of Kidney DiseasesVol. 54Issue 5PreviewStevens et al1 suggest that the Modification of Diet in Renal Disease (MDRD) Study equation for estimated glomerular filtration rate (GFR) is an acceptable substitute for estimated or measured creatinine clearance (CCr) as an index for adjusting drug doses in patients with chronic kidney disease and acute kidney injury. However, others have raised concerns that injudicious use of estimated GFR as a substitute for CCr could result in significant dosing errors and toxicity, especially for drugs with narrow therapeutic indices. Full-Text PDF Drug Dose Adjustments in Patients With Renal ImpairmentAmerican Journal of Kidney DiseasesVol. 54Issue 5PreviewWe read with interest the article by Stevens et al1 suggesting that the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation also can be used for drug dose adjustments and may be even more accurate in classifying patients into predefined glomerular filtration rate (GFR) ranges than the classic Cockcroft-Gault equation2 when using creatinine values standardized using isotope-dilution mass spectrometry. We agree that GFR estimates in units of milliliters per minute should be used for dose adjustment because it is expected that individual drug clearance (and consequently exposure to the drug) more closely correlates with absolute GFR, not with a normalized value. Full-Text PDF Use of the MDRD Study Equation for Drug DosingAmerican Journal of Kidney DiseasesVol. 54Issue 5PreviewWe appreciated the excellent article by Stevens et al1 on the comparison of drug dosing recommendations based on measured glomerular filtration rate– and kidney function–estimating equations. Although the study reflected a diverse population, it failed to provide detailed information about subgroups, including the elderly. Several studies have compared drug dosing recommendations based on the Cockcroft-Gault (CG) and the Modification of Diet in Renal Disease (MDRD) Study equations, finding higher values for glomerular filtration rate estimated using the MDRD Study equation and subsequently higher dosing recommendations. Full-Text PDF Estimated GFR for Drug Dosing: A Bedside FormulaAmerican Journal of Kidney DiseasesVol. 54Issue 5PreviewStevens et al1 showed that the Modification of Diet in Renal Diseases (MDRD) Study equation, after “uncorrection” of the body surface area (BSA) normalization to produce results in milliliters per minute rather than milliliters per 1.73 m2, provides a superior estimate of a formally measured glomerular filtration rate (GFR) in milliliters per minute than the Cockcroft-Gault formula,2 with fewer deviations in category assignment for drug dosing decisions. Full-Text PDF