Abstract

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.

Highlights

  • Acute kidney injury (AKI) is a common occurrence in hospitalized patients [1,2] and has been associated with increased mortality and longer length of stay [3]

  • The use of kinetic creatinine clearance (CrCl) and CKD-EPI estimated glomerular filtration rates (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

  • When we examined individual days for those with acute kidney injury (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

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Summary

Introduction

Acute kidney injury (AKI) is a common occurrence in hospitalized patients [1,2] and has been associated with increased mortality and longer length of stay [3]. During AKI, when SCr is fluctuating, standard estimates of creatinine clearance (CrCl) or estimated glomerular filtration rate (eGFR) are not valid, since these equations assume SCr is at steady state. Equations [4,5,6,7,8] that incorporate the rate of SCr change have been proposed to estimate instantaneous GFR during AKI. It is not necessarily surprising that keGFR is superior to standard estimates of renal function in predicting renal-centered outcomes since by definition, the former incorporates change in SCr, whereas the latter does not. In 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

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