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Updated: Aug 2, 2026
Isolation, Characterization, And High Throughput Extracellular Flux Analysis of Mouse Primary Renal Tubular Epithelial Cells
Published on: June 20, 2018
Development and Application of Human Renal Proximal Tubule Epithelial Cells for Assessment of Compound Toxicity
Shuaizhang Li1, Jinghua Zhao1, Ruili Huang1
19800 Medical Center Drive, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892-3375, USA.
Abstract:
Kidney toxicity is a major problem both in drug development and clinical settings. It is difficult to predict nephrotoxicity in part because of the lack of appropriate in vitro cell models, limited endpoints, and the observation that the activity of membrane transporters which plays important roles in nephrotoxicity by affecting the pharmacokinetic profile of drugs is often not taken into account. We developed a new cell model using pseudo-immortalized human primary renal proximal tubule epithelial cells. This cell line (SA7K) was characterized by the presence of proximal tubule cell markers as well as several functional properties, including transporter activity and response to a few well-characterized nephrotoxicants. We subsequently evaluated a group of potential nephrotoxic compounds in SA7K cells and compared them to a commonly used human immortalized kidney cell line (HK-2). Cells were treated with test compounds and three endpoints were analyzed, including cell viability, apoptosis and mitochondrial membrane potential. The results showed that most of the known nephrotoxic compounds could be detected in one or more of these endpoints. There were sensitivity differences in response to several of the chemicals between HK-2 and SA7K cells, which may relate to differences in expressions of key transporters or other components of nephrotoxicity pathways. Our data suggest that SA7K cells appear as promising for the early detection of renal toxicants.
Insights
A new human kidney cell model (SA7K) effectively detects drug-induced nephrotoxicity. This model shows promise for early identification of kidney toxicants in drug development, improving safety assessments.
Area of Science:
- Nephrology
- Toxicology
- Cell Biology
Background:
- Kidney toxicity (nephrotoxicity) poses significant challenges in drug development and clinical practice.
- Predicting nephrotoxicity is hindered by inadequate in vitro cell models and limited endpoints.
- The role of membrane transporters in drug pharmacokinetics and nephrotoxicity is often overlooked.
Purpose of the Study:
- To develop and characterize a novel pseudo-immortalized human renal proximal tubule epithelial cell line (SA7K) for nephrotoxicity assessment.
- To evaluate the utility of the SA7K cell line in detecting known nephrotoxicants.
- To compare the SA7K cell line's performance against a standard immortalized kidney cell line (HK-2).
Main Methods:
- Development of a pseudo-immortalized human primary renal proximal tubule epithelial cell line (SA7K).
- Characterization of SA7K cells for proximal tubule markers and functional transporter activity.
- Treatment of SA7K and HK-2 cells with various compounds and analysis of cell viability, apoptosis, and mitochondrial membrane potential.
Main Results:
- SA7K cells exhibited proximal tubule cell markers and functional transporter activity.
- Most known nephrotoxic compounds were detected using SA7K cells across multiple endpoints.
- Sensitivity differences were observed between SA7K and HK-2 cells, potentially due to variations in transporter expression.
Conclusions:
- The SA7K cell line demonstrates potential as a valuable tool for early detection of renal toxicants.
- This novel cell model may improve the prediction of drug-induced nephrotoxicity.
- Further investigation into transporter expression differences could elucidate mechanisms of differential sensitivity.
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