Department of Pharmacy, Kyushu University Hospital, Fukuoka 812-8582, Japan.
Department of Pharmacy, Kyushu University Hospital, Fukuoka 812-8582, Japan; Department of Clinical Pharmacology and Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan; Department of Pharmacy, International University of Health and Welfare Narita Hospital, Japan; Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, International University of Health and Welfare Narita Hospital, Japan.
Biochem Pharmacol. 2019 Dec;170:113664. doi: 10.1016/j.bcp.2019.113664. Epub 2019 Oct 10.
Several biomarkers are used to monitor organ damage caused by drug toxicity. Traditional markers of kidney function, such as serum creatinine and blood urea nitrogen are commonly used to estimate glomerular filtration rate. However, these markers have several limitations including poor specificity and sensitivity. A number of serum and urine biomarkers have recently been described to detect kidney damage caused by drugs such as cisplatin, gentamicin, vancomycin, and tacrolimus. Neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid-binding protein (L-FABP), kidney injury molecule-1 (KIM-1), monocyte chemotactic protein-1 (MCP-1), and cystatin C have been identified as biomarkers for early kidney damage. Hy's Law is widely used as to predict a high risk of severe drug-induced liver injury caused by drugs such as acetaminophen. Recent reports have indicated that glutamate dehydrogenase (GLDH), high-mobility group box 1 (HMGB-1), Keratin-18 (k18), MicroRNA-122 and ornithine carbamoyltransferase (OCT) are more sensitive markers of hepatotoxicity compared to the traditional markers including the blood levels of amiotransferases and total bilirubin. Additionally, the rapid development of proteomic technologies in biofluids and tissue provides a new multi-marker panel, leading to the discovery of more sensitive biomarkers. In this review, an update topics of biomarkers for the detection of kidney or liver injury associated with pharmacotherapy.
有几种生物标志物可用于监测药物毒性引起的器官损伤。传统的肾功能标志物，如血清肌酐和血尿素氮，常用于估计肾小球滤过率。然而，这些标志物存在一些局限性，包括特异性和灵敏度差。最近描述了许多血清和尿液生物标志物，用于检测顺铂、庆大霉素、万古霉素和他克莫司等药物引起的肾脏损伤。中性粒细胞明胶酶相关脂质运载蛋白 (NGAL)、肝型脂肪酸结合蛋白 (L-FABP)、肾损伤分子-1 (KIM-1)、单核细胞趋化蛋白-1 (MCP-1) 和胱抑素 C 已被确定为早期肾脏损伤的生物标志物。Hy's 法则被广泛用于预测乙酰氨基酚等药物引起的严重药物性肝损伤的高风险。最近的报告表明，与传统的生物标志物（包括氨基转移酶和总胆红素的血液水平）相比，谷氨酸脱氢酶 (GLDH)、高迁移率族蛋白 B1 (HMGB-1)、角蛋白-18 (k18)、MicroRNA-122 和鸟氨酸氨甲酰转移酶 (OCT) 是更敏感的肝毒性标志物。此外，生物体液和组织中蛋白质组学技术的快速发展提供了新的多标志物面板，从而发现了更敏感的生物标志物。在这篇综述中，更新了与药物治疗相关的肾或肝损伤的生物标志物检测的相关主题。
