Department of Pharmacy, Mayo Clinic, Rochester, MN; Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN.
Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN; Division of Epidemiology, Mayo Clinic, Rochester, MN.
Mayo Clin Proc. 2019 Mar;94(3):500-514. doi: 10.1016/j.mayocp.2018.08.002. Epub 2019 Jan 31.
Serum cystatin C has been proposed as a kidney biomarker to inform drug dosing. We conducted a systematic review to synthesize available data for the association between serum cystatin C and drug pharmacokinetics, dosing, and clinical outcomes in adults (≥18 years). PubMed, Ovid MEDLINE, Ovid EMBASE, EBSCO CINAHL, and Scopus were systematically searched from 1946 to September 2017 to identify candidate studies. Studies of cystatin C as a predictor for acute kidney injury or for management of contrast-associated acute kidney injury were excluded. Also, studies were excluded if drug concentrations were unavailable and if a reference standard for drug dosing (eg, serum creatinine) was not concurrently reported. The outcomes of interest included drug clearance (L/h), concentrations (mg/L), target level achievement (%), therapeutic failure (%), and drug toxicity (%). We included 28 articles that evaluated 16 different medications in 3455 participants. Vancomycin was the most well-studied drug. Overall, cystatin C-based estimated glomerular filtration rate (eGFR) was more predictive of drug levels and drug clearance than eGFR. In only one study were target attainment and outcomes compared between 2 drug-dosing regimens, one based on eGFR and one dosed with the Cockcroft-Gault creatinine clearance equation. Compared with eGFR, use of eGFR to predict elimination of medications via the kidney was as accurate, if not superior, in most studies, but infrequently were data on target attainment or clinical outcomes reported. Drug-specific dosing protocols that use cystatin C to estimate kidney function should be tested for clinical application.
血清胱抑素 C 已被提议作为一种肾脏生物标志物,用于指导药物剂量。我们进行了一项系统综述,以综合现有数据,评估血清胱抑素 C 与成年人(≥18 岁)药物药代动力学、剂量和临床结局之间的相关性。我们系统地检索了 1946 年至 2017 年 9 月期间的 PubMed、Ovid MEDLINE、Ovid EMBASE、EBSCO CINAHL 和 Scopus,以确定候选研究。排除了将胱抑素 C 作为急性肾损伤预测因子或用于管理对比相关急性肾损伤的研究。此外,如果无法获得药物浓度且未同时报告药物剂量的参考标准(如血清肌酐),则排除这些研究。感兴趣的结局包括药物清除率(L/h)、浓度(mg/L)、目标水平达标率(%)、治疗失败率(%)和药物毒性(%)。我们纳入了 28 篇评估了 3455 名参与者的 16 种不同药物的研究。万古霉素是研究最多的药物。总体而言,基于胱抑素 C 的估计肾小球滤过率(eGFR)比 eGFR 更能预测药物水平和药物清除率。只有一项研究比较了两种药物剂量方案的达标率和结局,一种方案基于 eGFR,另一种方案基于 Cockcroft-Gault 肌酐清除率方程进行剂量调整。与 eGFR 相比,在大多数研究中,使用 eGFR 预测药物经肾脏消除的准确性相当,甚至更优,但很少有关于达标率或临床结局的数据报告。应该对基于胱抑素 C 估计肾功能的药物特异性剂量方案进行临床试验检验。