Impact of Serum Cystatin C-Based Glomerular Filtration Rate Estimates on Drug Dose Selection in Hospitalized Patients

Study ObjectiveSerum creatinine (S-cr) concentration is used to calculate estimated glomerular filtration rate (eGFR) for medication dosing. Serum cystatin C (CysC) concentration has been proposed as an adjunct or alternative to S-cr. This study sought to evaluate the possible impact of using CysC in eGFR equations on drug dose recommendations in hospitalized patients with infections. DesignRetrospective analysis of prospectively collected data. SettingLarge academic tertiary care medical center. PatientsA total of 308 adults with suspected or documented infections and stable kidney function who were hospitalized between 2012 and 2015. Measurements and Main ResultsStandardized S-cr and CysC measured at the time of antibiotic dosing were used to estimate GFR from the three Chronic Kidney Disease Epidemiology Collaborative (CKD-EPI) equations using S-cr (eGFR(Cr)), CysC(eGFR(CysC)), or a combination of S-cr and CysC (eGFR(Cr-CysC)), and these values were compared with estimated creatinine clearance (eCl(cr)) from the Cockcroft-Gault equation (standard of care for drug dosage adjustments). The eGFRs were categorized into five common dosage adjustment strata (lower than 20, 20-49, 50-79, 80-130, and higher than 130 ml/min), and agreement between equations was tested with the weighted statistic. Recommended drug doses varied considerably between the eCl(cr) and the CKD-EPI equations (weighted [95% confidence interval]: eGFR(Cr) 0.73 [0.68-0.79], eGFR(CysC) 0.42 [0.35-0.5], eGFR(Cr-CysC) 0.65 [0.6-0.71]). If eGFR(Cr,) eGFR(CysC), or eGFR(Cr-CysC) were used instead of eCl(cr) to dose drugs, 11%, 12%, and 8% of doses, respectively, would be higher, and 12%, 38%, and 24% of doses, respectively, would be lower. ConclusionSignificant discordance in drug doses was observed when the CKD-EPI equations were used in place of eCl(cr). When CysC was included in eGFR equations, recommended doses were often lower. Further study is needed to develop and test drug-specific dosing guidelines that incorporate alternate renal biomarkers and/or more contemporary eGFR equations.