Predictability of serum vancomycin concentrations using the kinetic estimated glomerular filtration rate formula for critically ill patients

Harada, Dai; Uchino, Shigehiko; Kawakubo, Takashi; Takinami, Masanori

doi:10.5414/cp203266

Cited by 3 publications

(6 citation statements)

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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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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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“…Together, these studies show that keGFR improves prediction and understanding of renal function in AKI when the serum creatinine is rapidly fluctuating. However, there are limited studies evaluating keGFR for the purposes of drug dosing[19,20]. Harada [19] et al compared measured vancomycin concentrations with predicted vancomycin concentrations derived using varying estimates of renal function, but the predicted concentration [34] was derived from CG CrCl, which will bias the results in favor of the CG equation.…”

Section: Discussionmentioning

confidence: 99%

“…However, there are limited studies evaluating keGFR for the purposes of drug dosing[19,20]. Harada [19] et al compared measured vancomycin concentrations with predicted vancomycin concentrations derived using varying estimates of renal function, but the predicted concentration [34] was derived from CG CrCl, which will bias the results in favor of the CG equation. Pharmacist-led medication dosing tends to use CG CrCl because the previous US Food and Drug Administration guidance on pharmacokinetic categories is based on CrCl.…”

Section: Discussionmentioning

confidence: 99%

“…Kinetic eGFR may have significant impact for medication dosing during the development of and recovery from AKI. To date, two studies [19,20] have investigated the use of keGFR in medication dosing, but neither has quantified the magnitude of changes that would occur if keGFR was substituted for traditional methods in medication dosing. Dose adjustment based on renal function has historically used Cockcroft-Gault (CG) CrCl, since this is what has been recommended by the Food and Drug Administration for drug dosing categories during the process of drug approval.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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BackgroundIn acute kidney injury (AKI), medication dosing based on Cockcroft-Gault creatinine clearance (CrCl) or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimated glomerular filtration rates (eGFR) are not valid when serum creatinine (SCr) is not in steady state. The aim of this study was to determine the impact of a kinetic estimating equation that incorporates fluctuations in SCrs on drug dosing in critically ill patients.MethodsWe used data from participants enrolled in the NIH Acute Respiratory Distress Syndrome Network Fluid and Catheters Treatment Trial to simulate drug dosing category changes with the application of the kinetic estimating equation developed by Chen. We evaluated whether kinetic estimation of renal function would change medication dosing categories (≥60, 30–59, 15–29, and <15mL/min) compared with the use of CrCl or CKD-EPI eGFR.ResultsThe use of kinetic CrCl and CKD-EPI eGFR resulted in a large enough change in estimated renal function to require medication dosing recategorization in 19.3% [95 CI 16.8%–21.9%] and 23.4% [95% CI 20.7%–26.1%] of participants, respectively. As expected, recategorization occurred more frequently in those with AKI. When we examined individual days for those with AKI, dosing discordance was observed in 8.5% of total days using the CG CrCl and 10.2% of total days using the CKD-EPI equation compared with the kinetic counterparts.ConclusionIn a critically ill population, use of kinetic estimates of renal function impacted medication dosing in a substantial proportion of AKI participants. Use of kinetic estimates in clinical practice should lower the incidence of medication toxicity as well as avoid subtherapeutic dosing during renal recovery.

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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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Predictability of serum vancomycin concentrations using the kinetic estimated glomerular filtration rate formula for critically ill patients

Abstract: The predictability of KeGFR formula did not show good accuracy in critically ill patients. .

Cited by 3 publications

References 0 publications

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

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

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

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

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Predictability of serum vancomycin concentrations using the kinetic estimated glomerular filtration rate formula for critically ill patients

Abstract: The predictability of KeGFR formula did not show good accuracy in critically ill patients. .

Cited by 3 publications

References 0 publications

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

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

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

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

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Product

Resources

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Abstract: The predictability of KeGFR formula did not show good accuracy in critically ill patients. .