ArticleThe AAPS journal2018
Nephrotoxicity and Kidney Transport Assessment on 3D Perfused Proximal Tubules.
Article in The AAPS journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
59 citing papers in PubMed, 2 syntheses or guidelines pooled it, 130 citations in OpenAlex.
- Biomarker selection and reporting architecture in human proximal tubularFrontiers in toxicology · 2026Pooled it
- A systematic review of kidney-on-a-chip-based models to study human renal (patho-)physiology.Disease models & mechanisms · 2023Pooled it
- Kidney organoids as models for hereditary kidney diseases: Toward precision medicine (Review).Experimental and therapeutic medicine · 2026Review
- Enhancing therapeutic strategies and drug development for patients with kidney disease.Expert opinion on drug safety · 2026Review
- Microphysiological Systems for Comorbidity Studies: Chronic Kidney Disease and Osteoarthritis.Advanced healthcare materials · 2025Review
- A Novel Human Distal Tubuloid-on-a-Chip Model for Investigating Sodium and Water Transport Mechanisms.Kidney360 · 2025Article
- Organ-Specific Strategies in Bioprinting: Addressing Translational Challenges in the Heart, Liver, Kidney, and Pancreas.Journal of functional biomaterials · 2025Review
- Human and rat renal proximal tubule in vitro models for ADME applications.Archives of toxicology · 2025Review
- Cell Ratio-Dependent Osteoblast-Endothelial Cell Crosstalk Promoting Osteogenesis-Angiogenesis Coupling via Regulation of Microfluidic Perfusion and Paracrine Signaling.Micromachines · 2025Article
- Proximal tubule-on-chip as a model for predicting cation transport and drug transporter dynamics.Scientific reports · 2025Article
- Utility of Induced Pluripotent Stem Cell-Based Microphysiological Systems for Drug Development and Testing.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Comparative analysis of the physiological and transport functions of various sources of renal proximal tubule cells under static and fluidic conditions in PhysioMimix T12 platform.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Advanced Kidney Models In Vitro Using the Established Cell Line Renal Proximal Tubular Epithelial/Telomerase Reverse Transcriptase1 for Nephrotoxicity Assays.Biomimetics (Basel, Switzerland) · 2024Article
- Characterizing Glomerular Barrier Dysfunction with Patient-Derived Serum in Glomerulus-on-a-Chip Models: Unveiling New Insights into Glomerulonephritis.International journal of molecular sciences · 2024Article
- Allogeneic bone marrow mesenchymal stem cell-derived exosomes alleviate human hypoxic AKI-on-a-Chip within a tight treatment window.Stem cell research & therapy · 2024Article
- Development of Drug Efficacy Testing Platform for Glomerulonephritis.Micromachines · 2024Article
- A comprehensive review on 3D tissue models: Biofabrication technologies and preclinical applications.Biomaterials · 2024Review
- Organ-on-a-chip platforms for drug development, cellular toxicity assessment, and disease modeling.Turkish journal of biology = Turk biyoloji dergisi · 2024Review
- In-vivo and in-vitro toxicity evaluation of 2,3-dimethylquinoxaline: An antimicrobial found in a traditional herbal medicine.PloS one · 2024Article
- Precision nephrotoxicity testing using 3D in vitro models.Cell & bioscience · 2023Review
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proximal tubules in the kidney play a crucial role in reabsorbing and eliminating substrates from the body into the urine, leading to high local concentrations of xenobiotics. This makes the proximal tubule a major target for drug toxicity that needs to be evaluated during the drug development process. Here, we describe an advanced in vitro model consisting of fully polarized renal proximal tubular epithelial cells cultured in a microfluidic system. Up to 40 leak-tight tubules were cultured on this platform that provides access to the basolateral as well as the apical side of the epithelial cells. Exposure to the nephrotoxicant cisplatin caused a dose-dependent disruption of the epithelial barrier, a decrease in viability, an increase in effluent LDH activity, and changes in expression of tight-junction marker zona-occludence 1, actin, and DNA-damage marker H2A.X, as detected by immunostaining. Activity and inhibition of the efflux pumps P-glycoprotein (P-gp) and multidrug resistance protein (MRP) were demonstrated using fluorescence-based transporter assays. In addition, the transepithelial transport function from the basolateral to the apical side of the proximal tubule was studied. The apparent permeability of the fluorescent P-gp substrate rhodamine 123 was decreased by 35% by co-incubation with cyclosporin A. Furthermore, the activity of the glucose transporter SGLT2 was demonstrated using the fluorescent glucose analog 6-NBDG which was sensitive to inhibition by phlorizin. Our results demonstrate that we developed a functional 3D perfused proximal tubule model with advanced renal epithelial characteristics that can be used for drug screening studies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.