ArticleThe AAPS journal2016
A Human Renal Proximal Tubule Cell Line with Stable Organic Anion Transporter 1 and 3 Expression Predictive for Antiviral-Induced Toxicity.
Article in The AAPS journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 123 citations in OpenAlex.
- Transition to fetal calf serum-free culture enhances kidney proximal tubule cell bioenergetics and allows pharmacological applications.Cell and tissue research · 2026Article
- Evaluating the Utility and Constraints of the Competitive Counter Flow (CCF) Assay in OATP1B1 Substrate Profiling.The AAPS journal · 2026Article
- Rat and human primary proximal tubule epithelial cells allow for cross-species comparisons of drug-induced nephrotoxicity in vitro.Archives of toxicology · 2026Article
- Flavonoid Interactions with Renal Organic Anion Transporters OAT1 and OAT3: Structure-Activity Relationships and Clinical Implications.International journal of molecular sciences · 2026Review
- Advances and continuing challenges in differentiation of stem cells to human kidney tissue.Nature reviews. Nephrology · 2026Review
- Lack of Modulation of In Vivo Activity of Organic Anion Transporters 1 and 3 in Pregnancy Using Furosemide as a Probe.Journal of clinical pharmacology · 2026Article
- 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
- Human and rat renal proximal tubule in vitro models for ADME applications.Archives of toxicology · 2025Review
- hTERT and SV40LgT Renal Cell Lines Adjust Their Transcriptional Responses After Copy Number Changes from the Parent Proximal Tubule Cells.International journal of molecular sciences · 2025Article
- Comparative Analysis of Proximal Tubule Cell Sources for In Vitro Studies of Renal Proximal Tubule Toxicity.Biomedicines · 2025Article
- The Chorioallantoic Membrane as a Platform for Developing Vascularized Cell Macroencapsulation Devices.Journal of tissue engineering and regenerative medicine · 2025Article
- Efficient proximal tubule-on-chip model from hiPSC-derived kidney organoids for functional analysis of renal transporters.iScience · 2024Article
- Albumin-Mediated Drug Uptake by Organic Anion Transporter 1/3 Is Real: Implications for the Prediction of Active Renal Secretion Clearance.Molecular pharmaceutics · 2024Article
- Article
- Delivery and Transcriptome Assessment of an In Vitro Three-Dimensional Proximal Tubule Model Established by Human Kidney 2 Cells in Clinical Gelatin Sponges.International journal of molecular sciences · 2023Article
- Bioengineered Kidney Tubules Efficiently Clear Uremic Toxins in Experimental Dialysis Conditions.International journal of molecular sciences · 2023Article
- Portable, wearable and implantable artificial kidney systems: needs, opportunities and challenges.Nature reviews. Nephrology · 2023Review
- Cell and gene therapy for kidney disease.Nature reviews. Nephrology · 2023Review
- Metabolic impact of genetic and chemical ADP/ATP carrier inhibition in renal proximal tubule epithelial cells.Archives of toxicology · 2023Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Drug-induced nephrotoxicity still hampers drug development, because current translation from in vitro or animal studies to human lacks high predictivity. Often, renal adverse effects are recognized only during clinical stages of drug development. The current study aimed to establish a robust and a more complete human cell model suitable for screening of drug-related interactions and nephrotoxicity. In addition to endogenously expressed renal organic cation transporters and efflux transporters, conditionally immortalized proximal tubule epithelial cells (ciPTEC) were completed by transduction of cells with the organic anion transporter (OAT) 1 or OAT3. Fluorescence-activated cell sorting upon exposure to the OAT substrate fluorescein successfully enriched transduced cells. A panel of organic anions was screened for drug-interactions in ciPTEC-OAT1 and ciPTEC-OAT3. The cytotoxic response to the drug-interactions with antivirals was further examined by cell viability assays. Upon subcloning, concentration-dependent fluorescein uptake was found with a higher affinity for ciPTEC-OAT1 (Km = 0.8 ± 0.1 μM) than ciPTEC-OAT3 (Km = 3.7 ± 0.5 μM). Co-exposure to known OAT1 and/or OAT3 substrates (viz. para-aminohippurate, estrone sulfate, probenecid, furosemide, diclofenac, and cimetidine) in cultures spanning 29 passage numbers revealed relevant inhibitory potencies, confirming the robustness of our model for drug-drug interactions studies. Functional OAT1 was directly responsible for cytotoxicity of adefovir, cidofovir, and tenofovir, while a drug interaction with zidovudine was not associated with decreased cell viability. Our data demonstrate that human-derived ciPTEC-OAT1 and ciPTEC-OAT3 are promising platforms for highly predictive drug screening during early phases of drug development.
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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.