Study objective: Serum creatinine (Scr ) 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 Scr . 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 Scr 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 Scr (eGFRCr ), CysC(eGFRCysC ), or a combination of Scr and CysC (eGFRCr-CysC ), and these values were compared with estimated creatinine clearance (eClcr ) 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 eClcr and the CKD-EPI equations (weighted κ [95% confidence interval]: eGFRCr 0.73 [0.68-0.79], eGFRCysC 0.42 [0.35-0.5], eGFRCr-CysC 0.65 [0.6-0.71]). If eGFRCr, eGFRCysC , or eGFRCr-CysC were used instead of eClcr 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 eClcr . 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.
Keywords: antibiotics; augmented renal clearance; biomarker; creatinine clearance; cystatin C; glomerular filtration rate.
© 2018 Pharmacotherapy Publications, Inc.