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

Study Objective: Serum creatinine (S_{c r}) 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. Design: Retrospective analysis of prospectively collected data. Setting: Large academic tertiary care medical center. Patients: A total of 308 adults with suspected or documented infections and stable kidney function who were hospitalized between 2012 and 2015. Measurements and Main Results: Standardized S_{c r} 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_{c r} (eGFR_Cr), CysC(eGFR_CysC), or a combination of S_{c r} 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 κ statistic. Recommended drug doses varied considerably between the eCl_cr and the CKD-EPI equations (weighted κ [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. Conclusion: Significant 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.