Comparative Analysis of Proximal Tubule Cell Sources for in vitro Studies of Renal Toxicity

The kidneys are essential for eliminating drugs and chemicals from the human body, with renal epithelial cells being particularly vulnerable to damage caused by xenobiotics and their metabolites. Predicting renal toxicity before clinical trials remains a pressing challenge, necessitating more predictive in vitro models. However, the abundance of commercially available renal proximal tubule epithelial cell (RPTEC) sources complicates the selection of the most predictive cell types. This study compared RPTEC sources, including primary cells (Lonza) and various RPTEC lines, such as ciPTECs (Cell4Pharma), TERT1/RPTECs (ATCC), and HEK293 (GenoMembrane), alongside HepG2 cells for specificity comparison. We tested these cells' responses to 12 drugs to evaluate their predictive capabilities. Cells were cultured in 96-well or 384-well plates and exposed to drugs for 72 hours at concentrations ranging from 0.3 to 300 µM. The CellTiterGlo® assay measured cell viability, and transcriptome data from unexposed cells analyzed gene expression profiles using the TempO-seq® S1500+ panel. Cell viability data determined points of departure (PODs), compared to human serum Cmax,free values to assess safety margins. Gene expression showed primary kidney cells closely matched the human kidney medulla, followed by TERT1 and ciPTEC lines, with HEK lines showing the least correlation. This study highlights differences among RPTEC sources and their utility in drug safety studies for the renal proximal tubule, emphasizing unique gene expression patterns related to metabolism, ion transport, and cell development, which are vital for improving predictive models in renal toxicity assessment.