The “Guidance for Industry: Pharmacokinetics in Patients with Impaired Renal Function — Study Design, Data Analysis, and Impact on Dosing and Labeling” from the US Food and Drug Administration (FDA) states that the method for assessment of kidney function that is most widely used in clinical practice ought to be the method used for adjustment of drug dosages  This guidance was written in 1998. At the time, the Cockcroft and Gault was widely used and the FDA provided this equation as an example an estimate that could be used. Since then, there have been several events which call into the question the continued yes of the Cockcroft and Gault.

  • The MDRD Study equation and more recently the CKD-EPI equation have been shown to be more accurate than the Cockcroft and Gault equation
  • The MDRD Study and CKD-EPI equations are now more widely reported automatically by clinical laboratories every time a creatinine is measured
  • Creatinine assays are standardized to reference methods. Both the MDRD Study and CKD-EPI have been expressed for these reference methods, but The Cockcroft and Gault has not.  The assay used to develop The Cockcroft and Gault was likely 10-20% higher than current methods, therefore use of estimated creatinine clearance calculated using the Cockcroft and Gault will lead to higher drug dosing recommendations than was intended in the original pharmacokinetic studies.
  • Multiple studies have compared the equations for their impact on drug dosages. In the few studies that compared estimated GFR from the various equations to measured GFR, the studies have shown that the MDRD Study or CKD-EPI equation had greater concordance with measured GFR than the Cockcroft and Gault.  One study of inpatients receiving aminoglycoside or vancomycin compared the area under the curve for actual drug levels to the eGFR and showed greater precision for the MDRD Study equation


For additional Information on drug dosing:

The National Kidney Disease Education Program (NKDEP)



Last Updated: July 2014