Using Kinetic eGFR for Drug Dosing in AKI: Concordance between Kinetic eGFR, Cockroft-Gault Estimated Creatinine Clearance, and MDRD eGFR for Drug Dosing Categories in a Pilot Study Cohort.

INTRODUCTION

Drug dosing in patients with acute kidney injury (AKI) is based on the Cockroft-Gault (CG) equation-derived estimated Creatinine clearance (CGeCrCl) for historical reasons due to the lack of a validated method for estimating glomerular filtration rate (GFR) when Cr is rapidly changing. The kinetic equation (kinetic estimated GFR [KeGFR]) estimates GFR for the nonsteady-state Cr level. It is being validated in patient cohorts and could potentially be used for drug dosing when the Cr level is in the nonsteady state.

OBJECTIVE

The aim of the study was to measure the concordance and the degree of agreement between KeGFR-, CGeCrCl, and MDRD eGFR-based drug dosing categories in patients with nonsteady Cr levels.

METHODS

In the pilot study published previously, 80 adult patients with a significant change in Cr level after admission to the acute medical ward were classified as per the Acute Kidney Injury Network (AKIN) criteria and compared to a KeGFR-based criterion. The CG equation and the MDRD equation were applied retrospectively to the same dataset, and the concordance of the eGFR categories between the 3 methods was studied. The 3 eGFR categories (<30, 30-49, and >50 mL/min) were chosen to reflect the frequently used drug dosing categories in patients with renal impairment.

RESULTS

The concordance between CGeCRCL and KeGFR for drug dosing categories was only 62%, with 27 (90%) of the 30 discordant subjects falling into a higher eGFR category when KeGFR was used. The agreement between KeGFR and CGeCrCl was also unsatisfactory. There was better concordance (75%), but the agreement was also not satisfactory between MDRD eGFR and KeGFR for the drug dosing categories.

CONCLUSIONS

In AKI, compared to CGeCrCL, using KeGFR may affect drug dosing significantly by changing the eGFR category. Further studies of KeGFR for drug dosing will need therapeutic drug monitoring and pharmacokinetic studies for validation.