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Updated: Apr 20, 2026
Development of Human Renal Tubular Epithelial Cell Primary Cultures in Monolayers and Three-Dimensional Conditions
Published on: June 13, 2025
Application of RPTEC/TERT1 cells for investigation of repeat dose nephrotoxicity: A transcriptomic study
Lydia Aschauer1, Alice Limonciel1, Anja Wilmes1
1Division of Physiology, Dept. of Physiology and Medical Physics, Innsbruck Medical University, Fritz-Pregl Strasse 3, 6020 Innsbruck, Austria.
Abstract:
The kidney is a major target organ for toxicity. Incidence of chronic kidney disease (CKD) is increasing at an alarming rate due to factors such as increasing population age and increased prevalence of heart disease and diabetes. There is a major effort ongoing to develop superior predictive models of renal injury and early renal biomarkers that can predict onset of CKD. In the EU FP7 funded project, Predict-IV, we investigated the human renal proximal tubule cells line, RPTEC/TERT1 for their applicability to long term nephrotoxic mechanistic studies. To this end, we used a tiered strategy to optimise dosing regimes for 9 nephrotoxins. Our final testing protocol utilised differentiated RPTEC/TERT1 cells cultured on filter inserts treated with compounds at both the apical and basolateral side, at concentrations not exceeding IC10, for 14 days in a 24 h repeat application. Transepithelial electrical resistance and supernatant lactate were measured over the duration of the experiments and genome wide transcriptomic profiles were assayed at day 1, 3 and 14. The effect of hypoxia was investigated for a subset of compounds. The transcriptomic data were analysed to investigate compound-specific effects, global responses and mechanistically informative signatures. In addition, several potential clinically useful renal injury biomarkers were identified.
Insights
Researchers evaluated human kidney cells (RPTEC/TERT1) for long-term toxicity studies. This approach identified potential biomarkers for predicting chronic kidney disease (CKD) onset and understanding nephrotoxicity mechanisms.
Area of Science:
- Nephrology
- Toxicology
- Cell Biology
Background:
- Chronic kidney disease (CKD) incidence is rising globally, driven by aging populations and comorbidities like diabetes and heart disease.
- Developing accurate predictive models for renal injury and early biomarkers for CKD onset is a critical unmet need in clinical nephrology.
Purpose of the Study:
- To assess the utility of the human renal proximal tubule cell line (RPTEC/TERT1) for long-term nephrotoxicity studies.
- To optimize testing protocols for evaluating nephrotoxins using RPTEC/TERT1 cells.
- To identify novel renal injury biomarkers and understand mechanisms of nephrotoxicity.
Main Methods:
- A tiered strategy was employed to optimize dosing for nine nephrotoxins.
- Differentiated RPTEC/TERT1 cells cultured on filter inserts were treated apically and basolaterally for 14 days at concentrations not exceeding IC10.
- Transepithelial electrical resistance, supernatant lactate, and genome-wide transcriptomic profiles were measured over time. Hypoxia effects were also investigated.
Main Results:
- An optimized 14-day repeat-application protocol using RPTEC/TERT1 cells was established.
- Transcriptomic analysis revealed compound-specific effects, global cellular responses, and mechanistically informative signatures.
- Several potential biomarkers for renal injury were identified, showing promise for clinical utility.
Conclusions:
- The RPTEC/TERT1 cell line is a viable model for long-term nephrotoxic mechanistic studies.
- The developed protocol and transcriptomic analysis provide insights into drug-induced kidney injury.
- Identified biomarkers warrant further investigation for early CKD prediction.
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