Multiplex optical urinalysis for early detection of drug-induced kidney injury

Drug-induced kidney injury (DIKI) is a significant contributor of both acute and chronic kidney injury and remains a major concern in drug development and clinical care. However, current clinical diagnostic methods often fail to accurately and timely detect nephrotoxicity. This study reports the dev...

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Main Authors: Cheng, Penghui, Miao, Qingqing, Huang, Jiaguo, Li, Jingchao, Pu, Kanyi
Other Authors: School of Chemical and Biomedical Engineering
Format: Journal Article
Language:English
Published: 2021
Subjects:
Online Access:https://hdl.handle.net/10356/152066
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author Cheng, Penghui
Miao, Qingqing
Huang, Jiaguo
Li, Jingchao
Pu, Kanyi
author2 School of Chemical and Biomedical Engineering
author_facet School of Chemical and Biomedical Engineering
Cheng, Penghui
Miao, Qingqing
Huang, Jiaguo
Li, Jingchao
Pu, Kanyi
author_sort Cheng, Penghui
collection NTU
description Drug-induced kidney injury (DIKI) is a significant contributor of both acute and chronic kidney injury and remains a major concern in drug development and clinical care. However, current clinical diagnostic methods often fail to accurately and timely detect nephrotoxicity. This study reports the development of activatable molecular urinary reporters (MURs) that are able to specifically detect urinary biomarkers including γ-glutamyl transferase (GGT), alanine aminopeptidase (AAP), and N-acetyl-β-d-glucosaminidase (NAG). By virtue of their discrete absorption and emission properties, the mixture of MURs can serve as a cocktail sensor for multiplex optical urinalysis in the mouse models of drug-induced acute kidney injury (AKI) and chronic kidney disease (CKD). The MURs cocktail not only detects nephrotoxicity earlier than the tested clinical diagnostic methods in drug-induced AKI and CKD mice models, but also possesses a higher diagnostic accuracy. Therefore, MURs hold great promise for detection of kidney function in both preclinical drug screening and clinical settings.
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spelling ntu-10356/1520662021-09-01T06:36:59Z Multiplex optical urinalysis for early detection of drug-induced kidney injury Cheng, Penghui Miao, Qingqing Huang, Jiaguo Li, Jingchao Pu, Kanyi School of Chemical and Biomedical Engineering Engineering::Chemical engineering Anatomy Fluorescence Drug-induced kidney injury (DIKI) is a significant contributor of both acute and chronic kidney injury and remains a major concern in drug development and clinical care. However, current clinical diagnostic methods often fail to accurately and timely detect nephrotoxicity. This study reports the development of activatable molecular urinary reporters (MURs) that are able to specifically detect urinary biomarkers including γ-glutamyl transferase (GGT), alanine aminopeptidase (AAP), and N-acetyl-β-d-glucosaminidase (NAG). By virtue of their discrete absorption and emission properties, the mixture of MURs can serve as a cocktail sensor for multiplex optical urinalysis in the mouse models of drug-induced acute kidney injury (AKI) and chronic kidney disease (CKD). The MURs cocktail not only detects nephrotoxicity earlier than the tested clinical diagnostic methods in drug-induced AKI and CKD mice models, but also possesses a higher diagnostic accuracy. Therefore, MURs hold great promise for detection of kidney function in both preclinical drug screening and clinical settings. Ministry of Education (MOE) Nanyang Technological University K.P. thanks the Nanyang Technological University (Start-Up grant: M4081627), Singapore Ministry of Education Academic Research Fund Tier 1 (2017-T1-002-134, RG147/17; 2019-T1-002-045, and RG125/19), and Academic Research Fund Tier 2 (MOE2018-T2-2-042) for financial support. 2021-09-01T06:36:59Z 2021-09-01T06:36:59Z 2020 Journal Article Cheng, P., Miao, Q., Huang, J., Li, J. & Pu, K. (2020). Multiplex optical urinalysis for early detection of drug-induced kidney injury. Analytical Chemistry, 92(8), 6166-6172. https://dx.doi.org/10.1021/acs.analchem.0c00989 0003-2700 https://hdl.handle.net/10356/152066 10.1021/acs.analchem.0c00989 32241110 2-s2.0-85084658361 8 92 6166 6172 en M4081627 017-T1-002-134 RG147/17 2019-T1-002-045 RG125/19 MOE2018-T2-2-042 Analytical Chemistry © 2020 American Chemical Society. All rights reserved.
spellingShingle Engineering::Chemical engineering
Anatomy
Fluorescence
Cheng, Penghui
Miao, Qingqing
Huang, Jiaguo
Li, Jingchao
Pu, Kanyi
Multiplex optical urinalysis for early detection of drug-induced kidney injury
title Multiplex optical urinalysis for early detection of drug-induced kidney injury
title_full Multiplex optical urinalysis for early detection of drug-induced kidney injury
title_fullStr Multiplex optical urinalysis for early detection of drug-induced kidney injury
title_full_unstemmed Multiplex optical urinalysis for early detection of drug-induced kidney injury
title_short Multiplex optical urinalysis for early detection of drug-induced kidney injury
title_sort multiplex optical urinalysis for early detection of drug induced kidney injury
topic Engineering::Chemical engineering
Anatomy
Fluorescence
url https://hdl.handle.net/10356/152066
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