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Discrepancies between the Cockcroft–Gault and Chronic Kidney Disease Epidemiology (CKD-EPI) Equations: Implications for Refining Drug Dosage Adjustment Strategies

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Abstract

Introduction

The dosages of many medications require adjustment for renal function. There is debate regarding which equation, the Chronic Kidney Disease Epidemiology (CKD-EPI) equation vs. the Cockcroft–Gault (CG) equation, should be recommended to estimate glomerular filtration rate.

Methods

We used a mathematical simulation to determine how patient characteristics influence discrepancies between equations and analyzed clinical data to demonstrate the frequency of such discrepancies in clinical practice. In the simulation, the modifiable variables were sex, age, serum creatinine, and weight. We considered estimated glomerular filtration rate results in mL/min, deindexed for body surface area, because absolute excretory function (rather than per 1.73 m2 body surface area) determines the rate of filtration of a drug at a given plasma concentration. An absolute and relative difference of maximum (±) 10 mL/min and 10 %, respectively, were considered concordant. Clinical data for patients aged over 60 years (n = 9091) were available from one hospital and 25 private laboratories.

Results

In the simulation, differences between the two equations were found to be influenced by each variable but age and weight had the biggest effect. Clinical sample data demonstrated concordance between CKD-EPI and CG results in 4080 patients (45 %). The majority of discordant results reflected a CG result lower than the CKD-EPI equation. With aging, the CG result became progressively lower than the CKD-EPI result. When weight increased, the opposite occurred.

Discussion

The choice of equation for excretory function adjustment of drug dosage will have different implications for patients of different ages and body habitus.

Conclusions

The optimum equation for drug dosage adjustment should be defined with consideration of individual patient characteristics.

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    Authors and Affiliations

    1. Division of Nephrology, Dialysis and Transplantation, CHU Sart Tilman, University of Liège (ULg-CHU), 4000, Liège, Belgium

      Pierre Delanaye & Antoine Bouquegneau

    2. Oriade Laboratory, Vizille, France

      Fabrice Guerber

    3. Division of Clinical Pharmacology, Center for Interdisciplinary Research on Medicines, University of Liège, Liège, Belgium

      André Scheen

    4. Sheffield Kidney Institute, Northern General Hospital and Department of Infection, Immunity and Cardiovascular Science, University of Sheffield, Sheffield, UK

      Timothy Ellam

    5. Biochemistry Laboratory, Grenoble University Hospital, Grenoble, France

      Dorra Guergour

    6. Division of Nephrology, Dialysis, Transplantation and Hypertension, CHU Hôpital Nord, University Jean Monnet, PRES Université de LYON, Saint-Etienne, France

      Christophe Mariat

    7. Department of Public Health and Primary Care, KU, Leuven Kulak, Kortrijk, Belgium

      Hans Pottel

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    Correspondence to Pierre Delanaye.

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    Pierre Delanaye, Fabrice Guerber, André Scheen, Timothy Ellam, Antoine Bouquegneau, Dorra Guergour, Christophe Mariat, and Hans Pottel declare that they have no conflict of interest that might be relevant to the contents of this manuscript.

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    H. Pottel and C. Mariat equally contributed as last senior author.

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    Delanaye, P., Guerber, F., Scheen, A. et al. Discrepancies between the Cockcroft–Gault and Chronic Kidney Disease Epidemiology (CKD-EPI) Equations: Implications for Refining Drug Dosage Adjustment Strategies. Clin Pharmacokinet 56, 193–205 (2017). https://doi.org/10.1007/s40262-016-0434-z

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