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      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

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          Abstract

          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 (/1.73m 2), (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 P 30% 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.

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          Most cited references122

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          Statistical methods for assessing agreement between two methods of clinical measurement.

          In clinical measurement comparison of a new measurement technique with an established one is often needed to see whether they agree sufficiently for the new to replace the old. Such investigations are often analysed inappropriately, notably by using correlation coefficients. The use of correlation is misleading. An alternative approach, based on graphical techniques and simple calculations, is described, together with the relation between this analysis and the assessment of repeatability.
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            Acute kidney injury, mortality, length of stay, and costs in hospitalized patients.

            The marginal effects of acute kidney injury on in-hospital mortality, length of stay (LOS), and costs have not been well described. A consecutive sample of 19,982 adults who were admitted to an urban academic medical center, including 9210 who had two or more serum creatinine (SCr) determinations, was evaluated. The presence and degree of acute kidney injury were assessed using absolute and relative increases from baseline to peak SCr concentration during hospitalization. Large increases in SCr concentration were relatively rare (e.g., >or=2.0 mg/dl in 105 [1%] patients), whereas more modest increases in SCr were common (e.g., >or=0.5 mg/dl in 1237 [13%] patients). Modest changes in SCr were significantly associated with mortality, LOS, and costs, even after adjustment for age, gender, admission International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis, severity of illness (diagnosis-related group weight), and chronic kidney disease. For example, an increase in SCr >or=0.5 mg/dl was associated with a 6.5-fold (95% confidence interval 5.0 to 8.5) increase in the odds of death, a 3.5-d increase in LOS, and nearly 7500 dollars in excess hospital costs. Acute kidney injury is associated with significantly increased mortality, LOS, and costs across a broad spectrum of conditions. Moreover, outcomes are related directly to the severity of acute kidney injury, whether characterized by nominal or percentage changes in serum creatinine.
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              Prediction of creatinine clearance from serum creatinine.

              A formula has been developed to predict creatinine clearance (Ccr) from serum creatinine (Scr) in adult males: (see article)(15% less in females). Derivation included the relationship found between age and 24-hour creatinine excretion/kg in 249 patients aged 18-92. Values for Ccr were predicted by this formula and four other methods and the results compared with the means of two 24-hour Ccr's measured in 236 patients. The above formula gave a correlation coefficient between predicted and mean measured Ccr's of 0.83; on average, the difference predicted and mean measured values was no greater than that between paired clearances. Factors for age and body weight must be included for reasonable prediction.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                5 March 2015
                2015
                : 10
                : 3
                : e0116403
                Affiliations
                [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
                The University of Tokyo, JAPAN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: WLE CK JFMW PAGMDS. Performed the experiments: WLE MW PAGMDS. Analyzed the data: WLE CK MW JFMW PAGMDS. Wrote the paper: WLE CK HJD MW JFMW PAGMDS.

                ‡ These authors also contributed equally to this work.

                Article
                PONE-D-14-40269
                10.1371/journal.pone.0116403
                4351004
                25741695
                76fcac89-6645-4d51-baaa-8577a446d1d4
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 8 September 2014
                : 9 December 2014
                Page count
                Figures: 3, Tables: 3, Pages: 31
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Custom metadata
                All data published in the paper are available from the studies included and the outcomes those papers reported.

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