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

PLOS ONE, Dec 2019

Background The Modification of Diet in Renal Disease (MDRD) formula is widely used in clinical practice to assess the correct drug dose. This formula is based on serum creatinine levels which might be influenced by chronic diseases itself or the effects of the chronic diseases. We conducted a systematic review to determine the validity of the MDRD formula in specific patient populations with renal impairment: elderly, hospitalized and obese patients, patients with cardiovascular disease, cancer, chronic respiratory diseases, diabetes mellitus, liver cirrhosis and human immunodeficiency virus. Methods and Findings We searched for articles in Pubmed published from January 1999 through January 2014. Selection criteria were (1) patients with a glomerular filtration rate (GFR) < 60 ml/min (/1.73m2), (2) MDRD formula compared with a gold standard and (3) statistical analysis focused on bias, precision and/or accuracy. Data extraction was done by the first author and checked by a second author. A bias of 20% or less, a precision of 30% or less and an accuracy expressed as P30% of 80% or higher were indicators of the validity of the MDRD formula. In total we included 27 studies. The number of patients included ranged from 8 to 1831. The gold standard and measurement method used varied across the studies. For none of the specific patient populations the studies provided sufficient evidence of validity of the MDRD formula regarding the three parameters. For patients with diabetes mellitus and liver cirrhosis, hospitalized patients and elderly with moderate to severe renal impairment we concluded that the MDRD formula is not valid. Limitations of the review are the lack of considering the method of measuring serum creatinine levels and the type of gold standard used. Conclusion In several specific patient populations with renal impairment the use of the MDRD formula is not valid or has uncertain validity.

A PDF file should load here. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a PDF plug-in installed and enabled in your browser.

Alternatively, you can download the file locally and open with any standalone PDF reader:

https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0116403&type=printable

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 - 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)


This is a preview of a remote PDF: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0116403&type=printable

Willemijn L. Eppenga, Cornelis Kramers, Hieronymus J. Derijks, Michel Wensing, Jack F. M. Wetzels, Peter A. G. M. De Smet. 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, PLOS ONE, 2015, 3, DOI: 10.1371/journal.pone.0116403