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

Bradley J. Peters, Andrew D. Rule, Kianoush B. Kashani, John C. Lieske, Kristin C. Mara, Ross A. Dierkhising, Erin F. Barreto

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Study Objective: Serum creatinine (Sc 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 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 Sc 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 Sc r (eGFRCr), CysC(eGFRCysC), or a combination of Sc r 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.

Original languageEnglish (US)
Pages (from-to)1068-1073
Number of pages6
JournalPharmacotherapy
Volume38
Issue number10
DOIs
StatePublished - Oct 2018

Keywords

  • antibiotics
  • augmented renal clearance
  • biomarker
  • creatinine clearance
  • cystatin C
  • glomerular filtration rate

ASJC Scopus subject areas

  • Pharmacology (medical)

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