Clinical prospects of biomarkers for the early detection and/or prediction of organ injury associated with pharmacotherapy

• Published in: Biochemical pharmacology 2019-12, Vol.170, p.113664, Article 113664
• Main Authors: Tajima, Soichiro, Yamamoto, Nanae, Masuda, Satohiro
• Format: Article
• Language: English
• Subjects: Adverse reaction; AKI; DILI; Pharmacokinetics; Safety biomarker
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/j.bcp.2019.113664

[Display omitted] 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.