April 1, 2014 (Vol. 34, No. 7)

Burdened with the demands of handling waste, the kidneys are particularly susceptible to drug-induced toxicity. So it’s no surprise that pharma companies are increasingly finding nephrotoxicity to be a major cause of failure of candidate compounds during drug development, aiding in the downward spiral toward organ failure. Therefore, biomarkers for early detection of kidney disease and kidney toxicity are critical—both for improving patient treatment options and determining whether there are safety issues with compounds in development.

The current standards for determining kidney toxicity—measuring levels of serum creatinine (SCr) and blood urea nitrogen (BUN)—lack the sensitivity and specificity needed for early detection in both patients and animal studies. Studies have shown that approximately two-thirds of kidney function may already be lost before either of these biomarkers start to increase.

Fortunately, the Predictive Safety Testing Consortium (PSTC)—a collaboration of the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), along with the Nephrotoxic Working Group (NWG)—has identified a new generation of biomarkers that provides more sensitive and earlier detection of kidney damage. Companies have since been using these new biomarkers to develop products to conquer the kidney toxicity problem.

For example, Myriad RBM collaborated with the PSTC to create biomarker panels that were instrumental in the success of the PSTC’s first set of studies to detail the regulatory qualification of kidney biomarkers for preclinical use in detecting drug-induced kidney injury. These have been named the Rat KidneyMAP and Human KidneyMAP. Because the Rat KidneyMAP can localize damage to a particular segment of the nephron or even sub-cellular locations, using it to screen drug candidates during preclinical toxicity studies is becoming standard practice

Myriad RBM also teamed up with Bio-Rad Laboratories to develop a set of multiplex immunoassays, the Bio-Plex Pro RBM kidney toxicity panels. These comprise six of the seven PSTC-approved biomarkers that address the need for early detection and characterization of kidney toxicity and injury during drug development. The assays are available as premixed off-the-shelf kits for investigators to test compounds in both preclinical animal models and human clinical trials. They offer robust and reliable quantification of proteins, in a simple workflow, in human, rat, and canine urine samples. In addition, the Bio-Plex Pro RBM assays enable the detection of multiple biomarkers in a single sample to reveal damage within hours of kidney injury.

Thanks to new biomarkers and new partnerships, companies are finding ways to make drug development safer and to improve patient treatment options in the fight against kidney toxicity.

Dominic Eisinger, Ph.D. ([email protected]), is director of strategic development at Myriad RBM

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