Advanced in vitro evaluation of drug-induced kidney injury using microphysiological systems in drug discovery and development
Drug-induced kidney injury (DIKI) is a major cause of acute kidney injury (AKI). Given concerns about animal welfare and the need for more accurate prediction of human events, there is an urgent need to develop an in vitro evaluation method for DIKI using human cells. Renal proximal tubular epitheli...
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| Published in | Drug metabolism and pharmacokinetics Vol. 61; p. 101056 |
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| Main Authors | , , |
| Format | Journal Article |
| Language | English |
| Published |
England
Elsevier Ltd
01.04.2025
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| Subjects | |
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| Abstract | Drug-induced kidney injury (DIKI) is a major cause of acute kidney injury (AKI). Given concerns about animal welfare and the need for more accurate prediction of human events, there is an urgent need to develop an in vitro evaluation method for DIKI using human cells. Renal proximal tubular epithelial cells (RPTECs) are the main targets of DIKI in drug discovery and development because of their abundant expression of drug transporters that contribute to renal-specific drug distribution. In general, physiological kidney function is significantly reduced in primary cell monolayer culture systems. However, with recent advances in cell engineering and regenerative medicine, human kidney-derived cell culture systems, with higher kidney function compared to conventional systems, have been established. For example, three-dimensional cultured RPTECs show enhanced expression of drug transporters and higher predictive performance than monolayer culture systems. The use of organs-on-a-chip with liver and kidney co-cultures also allows the detection of drug metabolite-induced nephrotoxicity. Kidney organoids differentiated from induced pluripotent stem cells (iPS) have also been established. In this review, we introduce a recently established renal cell culture system that includes a microphysiological system, and review the in vitro methods used to evaluate DIKI in RPTECs.
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| AbstractList | Drug-induced kidney injury (DIKI) is a major cause of acute kidney injury (AKI). Given concerns about animal welfare and the need for more accurate prediction of human events, there is an urgent need to develop an in vitro evaluation method for DIKI using human cells. Renal proximal tubular epithelial cells (RPTECs) are the main targets of DIKI in drug discovery and development because of their abundant expression of drug transporters that contribute to renal-specific drug distribution. In general, physiological kidney function is significantly reduced in primary cell monolayer culture systems. However, with recent advances in cell engineering and regenerative medicine, human kidney-derived cell culture systems, with higher kidney function compared to conventional systems, have been established. For example, three-dimensional cultured RPTECs show enhanced expression of drug transporters and higher predictive performance than monolayer culture systems. The use of organs-on-a-chip with liver and kidney co-cultures also allows the detection of drug metabolite-induced nephrotoxicity. Kidney organoids differentiated from induced pluripotent stem cells (iPS) have also been established. In this review, we introduce a recently established renal cell culture system that includes a microphysiological system, and review the in vitro methods used to evaluate DIKI in RPTECs.Drug-induced kidney injury (DIKI) is a major cause of acute kidney injury (AKI). Given concerns about animal welfare and the need for more accurate prediction of human events, there is an urgent need to develop an in vitro evaluation method for DIKI using human cells. Renal proximal tubular epithelial cells (RPTECs) are the main targets of DIKI in drug discovery and development because of their abundant expression of drug transporters that contribute to renal-specific drug distribution. In general, physiological kidney function is significantly reduced in primary cell monolayer culture systems. However, with recent advances in cell engineering and regenerative medicine, human kidney-derived cell culture systems, with higher kidney function compared to conventional systems, have been established. For example, three-dimensional cultured RPTECs show enhanced expression of drug transporters and higher predictive performance than monolayer culture systems. The use of organs-on-a-chip with liver and kidney co-cultures also allows the detection of drug metabolite-induced nephrotoxicity. Kidney organoids differentiated from induced pluripotent stem cells (iPS) have also been established. In this review, we introduce a recently established renal cell culture system that includes a microphysiological system, and review the in vitro methods used to evaluate DIKI in RPTECs. Drug-induced kidney injury (DIKI) is a major cause of acute kidney injury (AKI). Given concerns about animal welfare and the need for more accurate prediction of human events, there is an urgent need to develop an in vitro evaluation method for DIKI using human cells. Renal proximal tubular epithelial cells (RPTECs) are the main targets of DIKI in drug discovery and development because of their abundant expression of drug transporters that contribute to renal-specific drug distribution. In general, physiological kidney function is significantly reduced in primary cell monolayer culture systems. However, with recent advances in cell engineering and regenerative medicine, human kidney-derived cell culture systems, with higher kidney function compared to conventional systems, have been established. For example, three-dimensional cultured RPTECs show enhanced expression of drug transporters and higher predictive performance than monolayer culture systems. The use of organs-on-a-chip with liver and kidney co-cultures also allows the detection of drug metabolite-induced nephrotoxicity. Kidney organoids differentiated from induced pluripotent stem cells (iPS) have also been established. In this review, we introduce a recently established renal cell culture system that includes a microphysiological system, and review the in vitro methods used to evaluate DIKI in RPTECs. Drug-induced kidney injury (DIKI) is a major cause of acute kidney injury (AKI). Given concerns about animal welfare and the need for more accurate prediction of human events, there is an urgent need to develop an in vitro evaluation method for DIKI using human cells. Renal proximal tubular epithelial cells (RPTECs) are the main targets of DIKI in drug discovery and development because of their abundant expression of drug transporters that contribute to renal-specific drug distribution. In general, physiological kidney function is significantly reduced in primary cell monolayer culture systems. However, with recent advances in cell engineering and regenerative medicine, human kidney-derived cell culture systems, with higher kidney function compared to conventional systems, have been established. For example, three-dimensional cultured RPTECs show enhanced expression of drug transporters and higher predictive performance than monolayer culture systems. The use of organs-on-a-chip with liver and kidney co-cultures also allows the detection of drug metabolite-induced nephrotoxicity. Kidney organoids differentiated from induced pluripotent stem cells (iPS) have also been established. In this review, we introduce a recently established renal cell culture system that includes a microphysiological system, and review the in vitro methods used to evaluate DIKI in RPTECs. [Display omitted] |
| ArticleNumber | 101056 |
| Author | Ishiguro, Naoki Arakawa, Hiroshi Matsushita, Kohei |
| Author_xml | – sequence: 1 givenname: Hiroshi orcidid: 0000-0001-6773-7646 surname: Arakawa fullname: Arakawa, Hiroshi email: arakawa@p.kanazawa-u.ac.jp organization: Faculty of Pharmaceutical Sciences, Institute of Medical Pharmaceutical and Health Sciences, Kanazawa University, Kakuma-machi, Kanazawa, 920-1192, Japan – sequence: 2 givenname: Kohei surname: Matsushita fullname: Matsushita, Kohei organization: Division of Pathology, National Institute of Health Sciences, Kawasaki, Kanagawa, Japan – sequence: 3 givenname: Naoki surname: Ishiguro fullname: Ishiguro, Naoki organization: Pharmacokinetics and Non-Clinical Safety Department, Nippon Boehringer Ingelheim Co., Ltd., Kobe, Japan |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/40088574$$D View this record in MEDLINE/PubMed |
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| Keywords | In vitro method Spheroid Transporter Microphyiological system Kidney Drug-induced kidney injury |
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| SubjectTerms | Acute Kidney Injury - chemically induced Animals Cell Culture Techniques - methods Drug Development - methods Drug Discovery - methods Drug-induced kidney injury Humans In vitro method Induced Pluripotent Stem Cells Kidney Kidney Tubules, Proximal - drug effects Kidney Tubules, Proximal - metabolism Microphyiological system Microphysiological Systems Spheroid Transporter |
| Title | Advanced in vitro evaluation of drug-induced kidney injury using microphysiological systems in drug discovery and development |
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