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

Abstract

<b><i>Introduction:</i></b> 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. <b><i>Objective:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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. <b><i>Conclusions:</i></b> 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.

ISCCM Guidelines on Acute Kidney Injury and Renal Replacement Therapy

“… 69 Among the equations used to estimate GFR, MDRD-6 and modified Jelliffe's equations fared relatively better. 70 Currently, there is growing interest in the application of the concept of “Kinetic GFR” which takes into account the dynamic changes in GFR in critically ill patients. 70 Despite the limitations, creatinine-based diagnosis and classification of AKI have brought about standardization both in clinical and research front and have shown a strong association with patient-centered outcomes.…”

In creatinine kinetics, the glomerular filtration rate always moves the serum creatinine in the opposite direction

“…Now, the creatinine trajectory with all its slopes can be decoded into a kinetic GFR format that shows how the kidney function is evolving. Insight into the underlying kidney function by using the kinetic GFR has improved the diagnosis and treatment of patients who suffer from an acute kidney injury (AKI) (Bairy, 2020;Bairy et al, 2018;Dash et al, 2020;Dewitte et al, 2015;Endre et al, 2016;Khayat et al, 2019;Kwong et al, 2019;Latha et al, 2020;O'Sullivan & Doyle, 2017;Pianta et al, 2015;Yoshida et al, 2019). With creatinine kinetics being modeled mathematically, a question that naturally arises is how much does the [creatinine] change in response to a change in kinetic GFR?…”