Nephrotoxicity

Most drugs found to cause nephrotoxicity exert toxic effects by one or more common pathogenic mechanisms. These include altered intraglomerular hemodynamics, tubular cell toxicity, inflammation, crystal nephropathy, rhabdomyolysis, and thrombotic microan-giopathy. Several possible drug-induced kidney biomarkers are under investigation.

First set: KIM-1, urinary IL-18, TFF3, urinary NAG, urinary GST-alpha, urinary NGAL

Pre-clinical Kidney: Phase I

European Medicines Agency (EMA), US Food and Drug Administration (FDA), and Pharmaceuticals and Medical Devices Agency (PMDA) Japan issued following test, can be utilized on a voluntary basis.

First set: urinary beta2-microblobulin, urinary KIM-1, TFF-3

Second Set: Rat toxicology studies to monitor drug-induced kidney injury.

Third set: Serum cystatin c, RBP-4, GST-alpha, NAG, NGAL

Mechanistic toxicology

To understand mechanism of action, the following assay end points are offered by Drik:

Cell viability

• MTT
• Neutral red
• LDH

Cell death

• Propidium iodide
• Fluorojade B