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创新利用新型生物标志物提高肾清除和肾毒性药物的安全性。

Innovative Use of Novel Biomarkers to Improve the Safety of Renally Eliminated and Nephrotoxic Medications.

机构信息

Department of Pharmacy, Mayo Clinic, Rochester, Minnesota.

Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, Minnesota.

出版信息

Pharmacotherapy. 2018 Aug;38(8):794-803. doi: 10.1002/phar.2149. Epub 2018 Jul 13.

DOI:10.1002/phar.2149
PMID:29883532
Abstract

Over the last decade, the discovery of novel renal biomarkers and research on their use to improve medication effectiveness and safety has expanded considerably. Pharmacists are uniquely positioned to leverage this new technology for renal assessment to improve medication dosing and monitoring. Serum cystatin C is a relatively new, inexpensive, functional renal biomarker that responds more quickly to changing renal function than creatinine and is not meaningfully affected by age, sex, skeletal muscle mass, dietary intake, or deconditioning. Cystatin C has been proposed as an adjunct or alternative to creatinine for glomerular filtration rate assessment and estimation of drug clearance. Tissue inhibitor of metalloproteinase-2·insulin-like growth factor-binding protein 7 ([TIMP-2]·[IGFBP7]) is a composite of two damage biomarkers released into the urine at a checkpoint in mitosis when renal cells undergo stress or sense a future risk of damage. Concentrations of [TIMP-2]·[IGFBP7] increase before a rise in serum creatinine is evident, thus providing insightful information for evaluation in the context of other patient data to predict the risk for impending kidney injury. This article provides a brief overview of novel renal biomarkers being used as a mechanism to improve medication safety including a discussion of cystatin C, as part of drug-dosing algorithms and specifically for vancomycin dosing, and the use of [TIMP-2]·[IGFBP7] for risk prediction in acute kidney injury and drug-induced kidney disease. Select cases of clinical experience with novel renal biomarkers are outlined, and lessons learned and future applications are described.

摘要

在过去的十年中,新型肾脏生物标志物的发现及其在提高药物疗效和安全性方面的应用研究取得了长足的发展。药剂师具有独特的优势,可以利用这种新型肾脏评估技术来改善药物剂量和监测。血清胱抑素 C 是一种相对较新的、廉价的、功能性的肾脏生物标志物,它对肾功能变化的反应比肌酐更快,而且不受年龄、性别、骨骼肌量、饮食摄入或身体不适的影响。胱抑素 C 已被提议作为评估肾小球滤过率和估计药物清除率的肌酐的辅助或替代物。组织金属蛋白酶抑制剂-2·胰岛素样生长因子结合蛋白 7([TIMP-2]·[IGFBP7])是两种损伤生物标志物的复合物,当肾脏细胞受到压力或感觉到未来有损伤风险时,它们会在有丝分裂的一个检查点释放到尿液中。[TIMP-2]·[IGFBP7]的浓度在血清肌酐升高之前就会升高,因此在其他患者数据的背景下提供有洞察力的信息,用于预测即将发生的肾损伤的风险。本文简要概述了新型肾脏生物标志物被用作提高药物安全性的一种机制,包括讨论胱抑素 C,作为药物剂量算法的一部分,特别是用于万古霉素剂量调整,以及使用[TIMP-2]·[IGFBP7]预测急性肾损伤和药物性肾病的风险。概述了新型肾脏生物标志物的一些临床经验案例,并描述了经验教训和未来的应用。

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