984
ACKNOWLEDGEMENTS St. John’s University College of Pharmacy and Allied
Financial Disclosure: None.
REFERENCES
1. Stevens LA, Nolin TD, Richardson MM, et al. Compari-
son of drug dosing recommendations based on measured
GFR and kidney function estimating equations. Am J Kidney
Dis. 2009;54(1):33-42.
2. Cockcroft DW, Gault MH. Prediction of creatinine clear-
ance from serum creatinine. Nephron. 1976;16(1):31-41.
3. Schneider V, Henschel V, Tadjalli-Mehr K, Mansmann
U, Haefeli WE. Impact of serum creatinine measurement
error on dose adjustment in renal failure. Clin Pharmacol
Ther. 2003;74(5):458-467.
4. Mosteller RD. Simplified calculation of body-surface
area [letter]. N Engl J Med. 1987;317(17):1098.
© 2009 by the National Kidney Foundation, Inc.
doi:10.1053/j.ajkd.2009.07.025
USE OF THE MDRD STUDY EQUATION FOR
DRUG DOSING
To the Editor:
We appreciated the excellent article by Stevens et al1
on the comparison of drug dosing recommendations based
on measured glomerular filtration rate– and kidney func-
tion–estimating equations. Although the study reflected a
diverse population, it failed to provide detailed informa-
tion about subgroups, including the elderly. Several stud-
ies 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.2-4 A cross-sectional study of elderly
patients found that using the MDRD Study equation to
dose amantadine and digoxin would result in 20% and
32% less patients requiring dose adjustments, respec-
tively.2 A prospective observational study also found
discordance rates ranging from 22%-36%, resulting in
higher antimicrobial doses using the MDRD Study versus
CG equation.3 A large observational study reported a
difference in the proportion of patients requiring dose
adjustment of antithrombotic agents using the CG versus
MDRD Study equation (eptifibatide, 45.7% vs 27.3%;
enoxaparin, 19% vs 9.6%).4 Because most studies use
simulated methods, the clinical significance of the dosing
differences is uncertain in the absence of clinical out-
comes. In light of these findings, we cannot advocate use
of the MDRD Study equation interchangeably with the
CG equation in drug dosing. Using the CG equation for
drug dosing may be a safer practice, particularly in the
elderly.
Maha Saad, PharmD, CGP, BCPS
Manouchkathe Cassagnol, PharmD, CGP, BCPS
Correspondence
Health Professions
Queens, New York
ACKNOWLEDGEMENTS
Financial Disclosure: None.
REFERENCES
1. Stevens LA, Nolin TD, Richardson MM, et al. Compari-
son of drug dosing recommendations based on measured
GFR and kidney function estimating equations. Am J Kidney
Dis. 2009;54(1):33-42.
2. Gill J, Malyuk R, Djurdjev O, Levin A. Use of GFR
equations to adjust drug doses in an elderly multi-ethnic
group—a cautionary tale. Nephrol Dial Transplant. 2007;
22(10):2894-2899.
3. Golik M, Lawrence K. Comparison of dosing recom-
mendations for antimicrobial drugs based on two methods
for assessing kidney function: Cockcroft-Gault and Modifi-
cation of Diet in Renal Disease. Pharmacotherapy. 2008;
28(9):1125-1132.
4. Melloni C, Peterson ED, Chen AY, et al. Cockcroft-
Gault versus Modification of Diet in Renal Disease: impor-
tance of glomerular filtration rate formula for classification
of chronic kidney disease in patients with non-ST-segment
elevation acute coronary syndromes. J Am Coll Cardiol.
2008;51(10):991-996.
© 2009 by the National Kidney Foundation, Inc.
doi:10.1053/j.ajkd.2009.07.026
ESTIMATED GFR VS CREATININE CLEARANCE
FOR DRUG DOSING
To the Editor:
Stevens et al1 suggest that the Modification of Diet in
Renal Disease (MDRD) Study equation for estimated glomer-
ular 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 therapeu-
tic indices.2-4 Further, their conclusion is not supported by
results of 4 studies that showed that using the MDRD Study
equation instead of CCr estimates led to recommendations
for 30%-60% higher doses of digoxin, amantadine, and
various antimicrobials.5-8 Estimated GFR values have also
been shown to overestimate CCr in patients with measured
GFRs ⬍ 60 mL/min/1.73 m2 (⬍1 mL/s/1.73 m2), the popula-
tion most likely to require dose modification.
Stevens et al used a standard dose for a limited drug
subset based on measured GFR to compare doses obtained
using 2 estimation methods (MDRD Study equation and
CCr). This approach inherently favors the MDRD Study
Correspondence
equation, because that formula was derived from iothalamate-
measured GFR. The justification for using measured GFR as
the index for determining drug dose categories discounts the
many studies relating drug dosing to estimated CCr. Current
US Food and Drug Administration (FDA) guidance on pharma-
cokinetic studies in chronic kidney disease and product labeling
recommend dose modification categories based on CCr, not
estimated GFR. The authors also back-corrected the automated
estimated GFR result, reported in milliliters per minute per 1.73
m2, using calculated body surface area (BSA), to yield values in
milliliters per minute. This BSA-modified MDRD hasn’t been
validated and calculating BSA in clinical settings is inconve-
nient and unlikely to occur. Without back-correction, signifi-
cant dosing errors might occur.
We believe that until studies are conducted to assess the
relationship between GFR estimated by a given methodol-
ogy and a drug’s pharmacokinetic parameters and/or
pharmacodynamic end points, traditional methods should
be used.
Thomas C. Dowling, PharmD, PhD
University of Maryland
Baltimore, Maryland
Gary R. Matzke, PharmD
Virginia Commonwealth University
Richmond, Virginia
John E. Murphy, PharmD
University of Arizona
Tucson, Arizona
ACKNOWLEDGEMENTS
Financial Disclosure: None.
REFERENCES
1. Stevens LA, Nolin TD, Richardson MM, et al. Compari-
son of drug dosing recommendations based on measured
GFR and kidney function estimating equations. Am J Kidney
Dis. 2009;54(1):33-42.
2. Spruill WJ, Wade WE, Cobb HH. Estimating glomeru-
lar filtration rate with a Modification of Diet in Renal
Disease equation: implications for pharmacy. Am J Health-
Syst Pharm. 2007;64(9):652-660.
3. Wolowich WR, Raymo L, Rodriguez JC. Problems
with the use of the Modified Diet in Renal Disease formula
to estimate renal function. Pharmacotherapy. 2005;25(9):
1283-1285.
4. Bauer L. Creatinine clearance versus glomerular filtration
rate for the use of renal drug dosing in patients with kidney
dysfunction. Pharmacotherapy. 2005;25(9):1286-1287.
5. Wargo KA, Eiland EH, Hamm W, et al. Comparison of
the Modification of Diet in Renal Disease and Cockcroft-
Gault equations for antimicrobial dosage adjustments. Ann
Pharmacother. 2006;40(7-8):1248-1253.
6. Gill J, Malyuk R, Djurdjev O, Levin A. Use of GFR
equations to adjust drug doses in an elderly multi-ethnic
group: a cautionary tale. Nephrol Dial Transplant. 2007;
22(10):2894-2899.
7. Golik MV, Lawrence KR. Comparison of dosing rec-
ommendations for antimicrobial drugs based on two meth-
985
ods for assessing kidney function: Cockcroft-Gault and
Modification of Diet in Renal Disease. Pharmacotherapy.
2008;28(9):1125-1132.
8. Hermsen ED, Maiefski M, Florescu MC, et al. Com-
parison of the Modification of Diet in Renal Disease and
Cockcroft-Gault equations for dosing antimicrobials. Phar-
macotherapy. 2009;29(6):649-655.
© 2009 by the National Kidney Foundation, Inc.
doi:10.1053/j.ajkd.2009.08.015
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’
We agree with Dr Jones1 and Czock and colleagues2 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 Cassagnol3 on the impor-
tance of clinical outcomes in the evaluation of the appropri-
ateness 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 standard4,5 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 compar-
ing 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 Cassagnol3 and Dowling et al6 do not account for the
effect of variation in creatinine assays. Pharmacokinetic
studies performed and corresponding dosing recommenda-
tions 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 trans-
lated 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.7,8 Going forward, pharmacokinetic