NEPHROTOXICITY

PREDICTIVE TOXICOLOGY

Liver, heart, kidney and brain drug-induced toxicities currently account for more than 70% of drug attrition and drug withdrawal. Porsolt together with Fluofarma has developed a range of organ-specific cell-based assays to better predict the toxicity potential of drug candidates prior to in vivo studies.

NEPHROTOXICITY

The kidney plays an important role in the elimination of many drugs and their metabolites. Drug-induced nephrotoxicity is a widespread complication. Several drugs have been implicated, among them antibiotics, and particularly aminoglycosides. Fluofarma developed a range of nephrotoxicity assays in high-throughput format to provide an early assessment of nephrotoxic effects.

PRIMARY HUMAN RENAL TUBULAR CELLS IN MICROPLATE FORMAT

Renal tubular cells, in particular proximal tubule cells, are highly vulnerable to drug toxicity, because of their filtrating role, which exposes them to high-levels of circulating toxins.

At Fluofarma, predictive human-derived cellular systems have been selected to maximize the predictive power of our nephrotoxicity assays: 

> Primary human renal proximal tubule epithelial cells

> Human renal proximal tubule epithelial cell line (HK-2)

FUNCTIONAL NEPHROTOXICITY ASSAYS

At the cell level, key hallmarks of drug-induced renal injury include lysosomal phospholipid accumulation and cytolytic activity.

Fluofarma offers 3 automated cell-based assays to identify nephrotoxic compounds:

> Lysosomal activity assay

> Mitochondrial toxicity assay

> Kinetic cytolysis assay

MOLECULAR NEPHROTOXICITY ASSAYS

To further understand the mechanism of action of nephrotoxic compounds, Fluofarma offers to measure key markers involved in oxidative stress and detoxification processes by high-content imaging.