USC To Conduct Clinical Trials To Improve Diagnosis of Medication-Induced Kidney Injury

Portrait of Dr. Beringer and Dr. RaoThe Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium has awarded the USC School of Pharmacy a contract for $352,733 to conduct an observational study to evaluate biomarkers of aminoglycoside-induced kidney toxicity among patients with cystic fibrosis.

Associate professor Paul Beringer, PharmD, will lead the USC project in collaboration with co- investigator Adupa P. Rao, MD, assistant professor of clinical medicine at the Keck School of Medicine. Their study will focus on patients being treated with aminoglycoside antibiotics, typically used when patients are hospitalized due to a pulmonary exacerbation, a notable worsening of lung function. The aminoglycoside antibiotics have the potential to cause significant kidney injury.

According to the Foundation, the Biomarkers Consortium, a public-private research partnership, aims to “test new biomarkers that are more sensitive, and will establish better criteria for when kidney safety concerns should halt further testing of a drug.” While kidney toxicity of some drugs presents a serious problem for drug developers, the currently used biomarkers lack sensitivity and can occasionally produce false positives. This may cause a delayed identification of clinically significant kidney injury until the later stages of drug development, resulting in potential exposure to large numbers of patients enrolled in clinical trials and unnecessary expenditure of time and resources to conduct these large-scale trials.

The USC study will evaluate 20 novel proteins important to kidney damage and determine the sensitivity and specificity in predicting kidney injury in patients receiving aminoglycoside therapy. The study will recruit 75 patients with cystic fibrosis. This patient population is a target group for this study as they are typically treated with aminoglycosides when pulmonary exacerbations occur. Further, this condition warrants hospitalization, providing an opportunity to conduct the testing and determine biomarker efficiency.

“The availability of these improved biomarkers will provide a tremendous asset to clinicians providing a more real-time picture of the effects of drugs on the kidney allowing precise dose titration to avoid clinically significant kidney injury,” says Dr. Beringer who works with Dr. Rao at the USC Cystic Fibrosis Program which manages some 200 adult patients with the disease.

The national study project involves USC and the University of Minnesota focusing on cystic fibrosis patients taking aminoglycosides and Brigham and Women’s Hospital/Dana Farber Cancer Institute and the M.D. Anderson Cancer Center studying patients with head and neck cancer using cisplatin, a common chemotherapy.

“Patient safety is and must be our primary concern as we develop potential new medicines,” explained Gary Herman, M.D., Vice President, Early Stage Development at Merck Research Laboratories. “The FNIH Biomarker Consortium Kidney Safety project is critical to help identify biomarkers that improve the process of developing effective medicines that are safe to test and use with patients.”

According to a press release from the Foundation, “The project will enable the continued development of potentially valuable compounds across a number of therapeutic areas, such as cancer, cystic fibrosis and diabetes. The data generated from this project is aimed to advance regulatory acceptance of new biomarkers appropriate for monitoring kidney safety in the clinic. Importantly, this data will improve clinical diagnoses of drug induced kidney injury during drug development and patient therapy.”

Some 30,000 American children and adults have cystic fibrosis, a genetic disease.