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

Study objective: Serum 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.

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_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 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.