ArticleJournal of the American Society of Nephrology : JASN2016
A Quantitative Approach to Screen for Nephrotoxic Compounds In Vitro.
Article in Journal of the American Society of Nephrology : JASN, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 126 citations in OpenAlex.
- Biomarker selection and reporting architecture in human proximal tubularFrontiers in toxicology · 2026Pooled it
- Construction, evaluation, and applications of renal barrier-on-a-chip system.Bioactive materials · 2026Review
- Monitoring biological effects of somatic cell genome editing.Nature reviews. Genetics · 2026Review
- Advancing transcriptomics-based mechanistic assessment of nephrotoxicity in vitro using the human RPTEC/TERT1 TXG-MAPr gene co-expression network.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Effect of calcium oxalate microcrystals on kidney proximal tubule epithelial cell gene expression in microgravity.NPJ microgravity · 2025Article
- Microphysiological systems as an emerging in vitro approach for the evaluation of drug absorption, distribution, metabolism, and excretion and toxicity.Drug metabolism and disposition: the biological fate of chemicals · 2025Review
- Injured Proximal Tubular Epithelial Cells Lose Hepatocyte Nuclear Factor 4α Expression Crucial for Brush Border Formation and Transport.The American journal of pathology · 2025Article
- Comparative Analysis of Proximal Tubule Cell Sources for In Vitro Studies of Renal Proximal Tubule Toxicity.Biomedicines · 2025Article
- Review
- Kidney Disease Modeling with Organoids and Organs-on-Chips.Annual review of biomedical engineering · 2024Review
- Development of a kidney microphysiological system hardware platform for microgravity studies.NPJ microgravity · 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
- Organ-on-a-chip platforms for drug development, cellular toxicity assessment, and disease modeling.Turkish journal of biology = Turk biyoloji dergisi · 2024Review
- Construction, Features and Regulatory Aspects of Organ-chip for Drug Delivery Applications: Advances and Prospective.Current pharmaceutical design · 2024Review
- Development of a Kidney Microphysiological System Hardware Platform for Microgravity Studies.Research square · 2023Article
- Role of in vitro two-dimensional (2D) and three-dimensional (3D) cell culture systems for ADME-Tox screening in drug discovery and development: a comprehensive review.ADMET & DMPK · 2023Review
- A comprehensive review on advancements in tissue engineering and microfluidics toward kidney-on-chip.Biomicrofluidics · 2022Review
- Human iPSC-derived renal organoids engineered to report oxidative stress can predict drug-induced toxicity.iScience · 2022Article
- Functional Drug Screening using Kidney Cells On-A-Chip: Advances in Disease Modeling and Development of Biomarkers.Kidney360 · 2022Article
- Microphysiological systems in absorption, distribution, metabolism, and elimination sciences.Clinical and translational science · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
Nephrotoxicity due to drugs and environmental chemicals accounts for significant patient mortality and morbidity, but there is no high throughput in vitro method for predictive nephrotoxicity assessment. We show that primary human proximal tubular epithelial cells (HPTECs) possess characteristics of differentiated epithelial cells rendering them desirable to use in such in vitro systems. To identify a reliable biomarker of nephrotoxicity, we conducted multiplexed gene expression profiling of HPTECs after exposure to six different concentrations of nine human nephrotoxicants. Only overexpression of the gene encoding heme oxygenase-1 (HO-1) significantly correlated with increasing dose for six of the compounds, and significant HO-1 protein deregulation was confirmed with each of the nine nephrotoxicants. Translatability of HO-1 increase across species and platforms was demonstrated by computationally mining two large rat toxicogenomic databases for kidney tubular toxicity and by observing a significant increase in HO-1 after toxicity using an ex vivo three-dimensional microphysiologic system (kidney-on-a-chip). The predictive potential of HO-1 was tested using an additional panel of 39 mechanistically distinct nephrotoxic compounds. Although HO-1 performed better (area under the curve receiver-operator characteristic curve [AUC-ROC]=0.89) than traditional endpoints of cell viability (AUC-ROC for ATP=0.78; AUC-ROC for cell count=0.88), the combination of HO-1 and cell count further improved the predictive ability (AUC-ROC=0.92). We also developed and optimized a homogenous time-resolved fluorescence assay to allow high throughput quantitative screening of nephrotoxic compounds using HO-1 as a sensitive biomarker. This cell-based approach may facilitate rapid assessment of potential nephrotoxic therapeutics and environmental chemicals.
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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.