Individualizing Pharmacotherapy in Patients with Renal Impairment: The Validity of the Modification of Diet in Renal Disease Formula in Specific Patient Populations with a Glomerular Filtration Rate below 60 Ml/Min. A Systematic Review
March
Individualizing Pharmacotherapy in Patients with Renal Impairment: The Validity of the Modification of Diet in Renal Disease Formula in Specific Patient Populations with a Glomerular Filtration Rate below 60 Ml/Min. A Systematic Review
Willemijn L. Eppenga 0 1
Cornelis Kramers 0 1
Hieronymus J. Derijks 0 1
Michel Wensing 0 1
Jack F. M. Wetzels 0 1
Peter A. G. M. De Smet 0 1
0 1 Radboud University Medical Center, Radboud Institute for Health Sciences, IQ Healthcare , Nijmegen , The Netherlands , 2 Radboud University Medical Center, Department of Pharmacology and Toxicology , Nijmegen , The Netherlands , 3 Department of Clinical Pharmacy, Canisius Wilhelmina Hospital , Nijmegen , The Netherlands , 4 Hospital Pharmacy 'ZANOB' , 's-Hertogenbosch , The Netherlands , 5 Division of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University , Utrecht , The Netherlands , 6 Radboud University Medical Center, Department of Nephrology , Nijmegen , The Netherlands , 7 Radboud University Medical Center, Department of Pharmacy , Nijmegen , The Netherlands
1 Academic Editor: Tatsuo Shimosawa, The University of Tokyo , JAPAN
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Competing Interests: The authors have declared
that no competing interests exist.
Background
cirrhosis and human immunodeficiency virus.
Methods and Findings
Conclusion
In several specific patient populations with renal impairment the use of the MDRD formula is
not valid or has uncertain validity.
Introduction
Box 1. MDRD equations.
Although there is an ongoing debate on whether the MDRD formula can safely replace the
CG formula in drug dosing [20,23], the MDRD formula is now widely used in clinical practice
for drug dosing in various patient populations.[19,24,25] The aim of this article is to review
systematically the validity and limitations of the MDRD formula in specific patient populations
with a known glomerular filtration rate below 60 ml/min where adjustment of the
pharmacotherapy usually should take place.
Background
Endogenous creatinine production
Fig 1. Determinants of serum creatinine level.
Exogenous creatinine supply
Dietary intake of creatinine and creatine can be either unusually high (ingestion of cooked
meat, creatine supplementation) or unusually low (vegetarian diet).[4,26] This may lead to
underestimation and overestimation of the GFR, respectively.
Laboratory assay of serum creatinine
true serum creatinine level up to 20%.[3,34] Substances which interfere with the Jaffe assay and
may lead to an overestimation of serum creatinine levels include bilirubine, 5-aminolevulic
acid, and high dose of lactulose. High doses of furosemide may lead to an underestimation of
serum creatinine levels and cephalosporins may lead to both over- and underestimation of
serum creatinine levels.[35,36,37,38,39] Substances which interfere with the enzymatic assay
include dopamine, dobutamine, glucose and flucytosine.[26,35,36] These interferences may
lead to an underestimation of serum creatinine levels and therefore an overestimation of the
GFR, except for flucytosine. Flucytosine may overestimate serum creatinine levels with more
than 100% and therefore underestimate the GFR.[36]
In addition to interferences of certain drugs in the creatinine assays, there are also
differences in creatinine values between clinical laboratories due to differences in the creatinine
assays and their calibration. Therefore a uniform creatinine measurement and a universal known
calibration of the serum creatinine assays has led to the introduction of IDMS calibration.
[18,40]
Creatinine secretion
Methods
Search strategy
We performed a systematic search in the Pubmed database for published studies about the
validity of the MDRD formula in diverse patient populations. The search focused on publications
between January 1999 (the introduction of the MDRD formula [15]) and January 2014. We
searched for both the MDRD-4 and MDRD-6 formulas. The terms used for the overall search
strategy have been listed in S1 File.
Selection criteria
We focused on studies in patients with a measured GFR (mGFR) or estimated GFR (eGFR) <
60 ml/min(/1.73m2). Other selection criteria were (1) MDRD formula compared with a gold
standard (defined as: 99mTc-DTPA, inulin (including the analogue sinistrin[47]), 51Cr-EDTA,
125I-iothalamate and Iohexol) and (2) statistical analysis and reporting focused on bias,
precision and/or accuracy (see Table 1 for definitions).
We excluded case reports, abstracts, and posters. Articles which reproduced data already
published elsewhere were carefully reviewed. Only if newer data added information to our
review, the article was included.
Selection of patient population
Definition bias
Mean percentage difference
md eGFR-mGFR
md ((eGFR-mGFR)/mGFR) x 100%
1/n x (eGFR-mGFR)
1/n x ((eGFR-mGFR)/mGFR) x 100%
Formula
IQR of (eGFRmGFR)
IQR of ((eGFR-mGFR)/mGFR) x 100%
Mean difference 1.96 SD
of all the individual differences
Formula
Percentage (...truncated)