Department of Pharmacy, Mayo Clinic, Rochester, Minnesota.
Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota.
Pharmacotherapy. 2018 Oct;38(10):1068-1073. doi: 10.1002/phar.2175. Epub 2018 Sep 12.
Serum creatinine (S ) 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 . This study sought to evaluate the possible impact of using CysC in eGFR equations on drug dose recommendations in hospitalized patients with infections.
Retrospective analysis of prospectively collected data.
Large academic tertiary care medical center.
A total of 308 adults with suspected or documented infections and stable kidney function who were hospitalized between 2012 and 2015.
Standardized S 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 (eGFR ), CysC(eGFR ), or a combination of S and CysC (eGFR ), and these values were compared with estimated creatinine clearance (eCl ) 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 and the CKD-EPI equations (weighted κ [95% confidence interval]: eGFR 0.73 [0.68-0.79], eGFR 0.42 [0.35-0.5], eGFR 0.65 [0.6-0.71]). If eGFR eGFR , or eGFR were used instead of eCl to dose drugs, 11%, 12%, and 8% of doses, respectively, would be higher, and 12%, 38%, and 24% of doses, respectively, would be lower.
Significant discordance in drug doses was observed when the CKD-EPI equations were used in place of eCl . 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.
血清肌酐（S）浓度用于计算估计肾小球滤过率（eGFR）以进行药物剂量调整。血清胱抑素 C（CysC）浓度已被提议作为 S 的辅助或替代方法。本研究旨在评估在感染住院患者中使用 eGFR 方程中的 CysC 对药物剂量建议的可能影响。
前瞻性收集数据的回顾性分析。
大型学术三级保健医疗中心。
2012 年至 2015 年间，共 308 名疑似或确诊感染且肾功能稳定的成年人住院。
在使用抗生素时测量的标准化 S 和 CysC 用于根据三个慢性肾脏病流行病学合作（CKD-EPI）方程估计 GFR，使用 S（eGFR）、CysC（eGFR）或 S 和 CysC 的组合（eGFR），并将这些值与 Cockcroft-Gault 方程（药物剂量调整的标准）估计的肌酐清除率（eCl）进行比较。eGFR 分为五个常见的剂量调整亚组（低于 20、20-49、50-79、80-130 和高于 130 ml/min），并使用加权 κ 统计量检验方程之间的一致性。与 CKD-EPI 方程相比，eCl 和方程推荐的药物剂量差异很大（加权 κ [95%置信区间]：eGFR 0.73 [0.68-0.79]、eGFR 0.42 [0.35-0.5]、eGFR 0.65 [0.6-0.71]）。如果使用 eGFR、eGFR 或 eGFR 代替 eCl 来给药物剂量，分别有 11%、12%和 8%的剂量会更高，而分别有 12%、38%和 24%的剂量会更低。
当 CKD-EPI 方程代替 eCl 时，观察到药物剂量存在显著差异。当 CysC 被纳入 eGFR 方程时，推荐的剂量通常较低。需要进一步研究来开发和测试包含替代肾脏生物标志物和/或更现代的 eGFR 方程的特定药物剂量指南。
