It is estimated that drugs are responsible approximately 20% of acute renal failure episodes; this figure increases dramatically in the elderly where the incidence of drug-induced nephrotoxicity is reported to be as high as 66%1,2,3,4. This increased incidence in the elderly is thought to be a consequence of underlying conditions such as diabetes, cardiovascular disease and renal insufficiency as well as exposure to a greater number of co-administered drugs5.
The kidneys have a rich blood supply, have significant transporter activity and act as a highly structured filtration network. These features can result in the kidneys being exposed to high concentrations of drugs or metabolites, which ultimately increases their susceptibility to drug-induced toxicity6.
Due to the incidence of drug-induced nephrotoxicity, it is important to understand the risks of this liability prior to reaching the clinic. In vitro human cell-based kidney models using RPTECs (renal proximal tubule epithelial cells) are now becoming popular for early stage testing of nephrotoxicity. These are the predominant cells in the proximal kidney tubule, which is one of the main sites for reabsorption and drug accumulation.
Cyprotex offer a multiparametric high content screening (HCS) assay which evaluates the chronic exposure of test articles over 9 days and measures multiple relevant cell health markers including glutathione content (GSH), phospholipidosis (PLD), mitochondrial mass and mitochondrial membrane potential, as well as cellular ATP levels in a human kidney relevant in vitro cell-based model utilising RPTECs.
1 Kaufman J et al., (1991) Community-acquired acute renal failure. Am J Kidney Dis17(2): 191-198 2 Nash K et al., (2002) Hospital-acquired renal insufficiency. Am J Kidney Dis39(5): 930-936 3 Bellomo R (2006) The epidemiology of acute renal failure: 1975 versus 2005. Curr Opin Crit Care 12(6): 557-560 4 Kohli HS et al., (2000) Treatment-related acute renal failure in the elderly: a hospital-based prospective study. Nephrol Dial Transplant15(2): 212-217 5 Naughton CA (2008) Drug-induced nephrotoxicity. Am Fam Physician 78(6): 743-750