Kidney Specific Toxicity (KST) Screen
For a comprehensive evaluation of kidney toxicity with in vivo relevance.
Download Kidney Toxicity PDF
Drug-induced adverse effects in the kidney are a major reason for late stage attrition of promising new candidates. The ability to identify renal specific risk for toxicity early in the drug discovery process would greatly improve the probability of success in animal and human safety studies. In vitro models that can provide reliable information on expected adverse effects must consist of organ specific cells that maintain in vivo physiological functions. The biochemical or molecular endpoints measured must be unique to the organ of interest, and the origin of the test cells should be species-specific.
Renal specificity is achieved by 1) determining whether the cytotoxicity of the test compound is due to transporter uptake, and 2) determining toxicity in hRPTECs relative to hepatocytes. The probability that a test compound will produce renal toxicity over hepatotoxicity is determined by comparing general toxicity in human proximal tubule epithelial cells (hRPTECs) to toxicity in hepatocytes (Hep). The same exposure concentrations and times are used in both cell models. A mean TC50 value is determined across the endpoints measured in each cell type. The mean TC50 in hRPTECs is compared to the mean TC50 in Hep to determine the toxicity index (TI).
If TI = 1 then equal toxicity
If TI < 1 then kidney toxicity
If TI > 1 then liver toxicity
The kidney toxicity model is a cost-effective way to quickly identify kidney-specific toxicity using multiple biochemical endpoints and gene expression markers.