Bri Heron, technology marketing manager at Indiana University’s Innovation and Commercialization Office, contributed the following story.
Bruce Molitoris, MD, MS, a distinguished professor emeritus at the Indiana University School of Medicine and internationally acclaimed scientist, has determined that the Alpha-2-macroglubin Receptor Associated Protein, a naturally occurring protein inhibitor of kidney proximal tubule reabsorption, minimizes drug-induced kidney injury (nephrotoxicity), which is one of the main contributors behind acute kidney injury.
Acute kidney injury occurs in an estimated one in five adults and one in three children hospitalized with acute illness, and the incidence is increasing. Acute kidney injury develops rapidly and results in the kidney’s inability to remove waste products from the blood. Drugs that can cause acute kidney injury are termed nephrotoxins, and they lead to 20 percent of hospitalized cases of acute kidney injury. Therapeutic agents such as antibiotics, radiocontrast and cancer drugs are nephrotoxic. They are filtered by the kidney and reabsorbed and concentrated within proximal tubule cells, thus leading to cellular injury and acute kidney injury. There is currently no FDA-approved drug therapy for the prevention of acute kidney injury.
Currently, there are no treatments to inhibit proximal tubule reabsorption of potential toxins to prevent kidney injury. Molitoris and his team discovered that administering the receptor associated protein turned off reabsorption of a toxic antibiotic and minimized acute kidney injury.
“Being able to turn off proximal tubule reabsorption rapidly and reversibly is a major step forward in potentially preventing nephrotoxicity from any filtered drug,” said Molitoris. “This would allow clinicians to provide patients at a high risk for acute kidney injury potential nephrotoxic therapies and also provide higher doses of nephrotoxic drugs to others to improve efficacy while minimizing the side effect of acute kidney injury.”
In the study, Molitoris and colleagues used rat models to understand the impact of the receptor associated protein on aminoglycoside-induced acute kidney injury. They determined the inhibitor caused minimal change in kidney function, while those with the placebo developed severe acute kidney injury.
Based on these findings, Molitoris and his team determined that the receptor associated protein has the potential to be used to prevent drug induced acute kidney injury in patients in care situations such as hospitals, ICUs or infusion centers if it is given before administering the nephrotoxic agent.
The Molitoris team has disclosed several intentions with IU’s Innovation and Commercialization Office, and recently filed a patent to protect this research.
One of only a few international leaders in nephrology whose research focuses on acute kidney injury, Molitoris established and developed the Indiana Center for Biological Microscopy. Established in 1996, the center is now a vital research core facility supporting biomedical research needs of more than 100 laboratories in Indiana.
He has published over 100 original research papers and has received over $25 million in funded research support from the National Institutes of Health, Veterans Administration, American Heart Association and Lilly Pharmaceuticals. He also holds six patents and is the founding member and manager of INphoton, LLC, and cofounder of Pharmacophotonics (now FAST BioMedical).
More about Molitoris and his past pioneering research is available on IU’s University Honors and Awards website.