The value of kinetic glomerular filtration rate estimation on medication dosing in acute kidney injury

Kwong, Yuenting D.; Chen, Sheldon; Bouajram, Rima; Li, Fanny; Matthay, Michael A.; Mehta, Kala M.; Glidden, David V.; Liu, Kathleen D.

doi:10.1371/journal.pone.0225601

Cited by 23 publications

(17 citation statements)

References 34 publications

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“…One study of elderly people with stable renal function in a long-term care facility found a concordance of only 60% between the 2 methods [9]. Our findings are comparable to a recent study of participants with acute respiratory distress syndrome in which the use of KeGFR was shown to impact drug dosing in a quarter of all subjects, more so in patients with AKI compared to CGeCrCl and CKD-EPI GFR during the first week of admission [10].…”

Section: Discussion/conclusionsupporting

confidence: 72%

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

Bairy

2020

Nephron

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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.

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Section: Discussion/conclusionsupporting

confidence: 72%

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

Bairy

2020

Nephron

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“…Other options include approaches such as the kGFR equation, which has provided heterogeneous results when applied to drug dosing. [44][45][46] Potential limitations of kGFR include the use of baseline clearance and maximum change in SCr, which are subjective and might not be suitable in a clinical trial setting, and the inability to consider urine data. Again, a model-based approach seems preferable.…”

Section: Discussionmentioning

confidence: 99%

A Model‐Based Approach to Assess Unstable Creatinine Clearance in Critically Ill Patients

Ullah

Zöller

Jaehde

et al. 2021

Clin Pharma and Therapeutics

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Creatinine clearance is an important tool to describe the renal elimination of drugs in pharmacokinetic (PK) evaluations and clinical practice. In critically ill patients, unstable kidney function invalidates the steady-state assumption underlying equations, such as Cockcroft-Gault. Although measured creatinine clearance (mCrCL) is often used in nonsteady-state situations, it assumes that observed data are error-free, neglecting frequently occurring errors in urine collection. In contrast, compartmental nonlinear mixed effects models of creatinine allow to describe dynamic changes in kidney function while explicitly accounting for a residual error associated with observations. Based on 530 serum and 373 urine creatinine observations from 138 critically ill patients, a onecompartment creatinine model with zero-order creatinine generation rate (CGR) and first-order CrCL was evaluated. An autoregressive approach for interoccasion variability provided a distinct model improvement compared to a classical approach (Δ Akaike information criterion (AIC) −49.0). Fat-free mass, plasma urea concentration, age, and liver transplantation were significantly related to CrCL, whereas weight and sex were linked to CGR. The modelbased CrCL estimates were superior to standard approaches to estimate CrCL (or glomerular filtration rate) including Cockcroft-Gault, mCrCL, four-variable modification of diet in renal disease (MDRD), six-variable MDRD, and chronic kidney disease epidemiology collaboration as a covariate to describe cefepime and meropenem PKs in terms of objective function value. In conclusion, a dynamic model of creatinine kinetics provides the means to estimate actual CrCL despite dynamic changes in kidney function, and it can easily be incorporated into population PK evaluations.

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“…Table 2 describes the studies evaluating the KeGFR approach in critically ill patients, a population with frequently changing kidney function. 15,21-26 All the studies based the KeGFR calculations on the method of Chen. 10 Based on the results of these investigations, we suggest that standard methods be used when SCr is stable with only minor fluctuation.…”

Section: Studies Evaluating Kinetic Estimates Of Clearancementioning

confidence: 99%

Creatinine Assessment in Non–Steady-State Conditions: A Critical Review

Nix

Erstad

2021

Ann Pharmacother

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Objectives: To discuss methods for the assessment of creatinine clearance (Clcr) when serum creatinine (SCr) is not at steady state in order to estimate kidney function and apply the estimate to kidney function staging for clinical assessment or drug dosing. Data Sources: A PubMed search was conducted from 1976 to mid-January 2021 with other articles identified through review of bibliographies of retrieved articles and citations in Scopus. Study Selection and Data Extraction: Articles assessing Clcr under non–steady-state conditions and studies evaluating predictive equations were selected. Data Synthesis: When SCr is systematically changing (ie, trending up or down), kinetic methods to estimate Clcr are appropriate. Estimates from kinetic methods should be individual based and not indexed to body surface area, and careful monitoring is required to confirm predictions as the situation evolves. Standard methods intended for steady-state conditions should not be used to estimate Clcr in patients with unstable SCr. Relevance to Patient Care and Clinical Practice: Creatinine continues to be a monitoring parameter of choice and is an important variable in all the commonly used equations for estimating Clcr and most important for estimating glomerular filtration rate. However, standard methods of estimating Clcr for medication dosing are not accurate under non–steady-state conditions. Conclusion: The methods for kinetic clearance estimation and standards methods for clearance estimation, such as the Cockcroft-Gault equation, are mutually exclusive. There are no benefits of using the kinetic method in patients with stable SCr concentrations, and standard equations are not appropriate with unstable SCr concentrations.

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The value of kinetic glomerular filtration rate estimation on medication dosing in acute kidney injury

Cited by 23 publications

References 34 publications

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

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

A Model‐Based Approach to Assess Unstable Creatinine Clearance in Critically Ill Patients

Creatinine Assessment in Non–Steady-State Conditions: A Critical Review

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