15 Jun New Target Aims To Prevent Kidney Damage in Heart Failure Patients

MedicalResearch.com Interview with:

Dr. Burns Blaxall

Burns C. Blaxall, PhD, FAHA, FACC, FAPS
Director of Translational Science, Heart Institute
Co-Director, Heart Institute Research Core & Biorepository
Professor, UC Department of Pediatrics

MedicalResearch.com: What is the background for this study?

Dr. Blaxall: The development of kidney disease subsequent to chronic heart failure is known clinically as cardiorenal syndrome 2, and is associated with dual organ failure and reduced survival. Furthermore, patients undergoing invasive cardiac procedures that require heart-lung bypass are at significant risk for developing kidney injury. According to the National Kidney Foundation, cardiorenal syndrome 2 presents a considerable economic burden of around $30 billion annually. Previous work has demonstrated the role of G protein-coupled receptor (GPCR) signaling and the activation of G protein βγ (Gβγ) subunits in the development and progression of heart failure, however little is known regarding the role of this signaling pathway in kidney disease.

MedicalResearch.com: What are the main findings?

Dr. Blaxall:  These studies are the first to suggest that inhibition of pathologic GPCR-Gβγ signaling can prevent renal damage in a model of cardiorenal syndrome 2, as well as following acute kidney injury. It is now understood that chronic activation of GPCR-Gβγ signaling plays a significant role in the development of chronic and acute kidney disease. In this study, we have evaluated the novel small molecule inhibitor gallein, which targets pathologic GPCR-Gβγ signaling and has proven effective in several models of heart failure. Findings from this study have revealed the protective properties of gallein in mouse models of cardiorenal syndrome 2 and acute kidney injury, including reductions in renal fibrosis, inflammation, tissue damage and dysfunction.

MedicalResearch.com: What should readers take away from your report?

Dr. Blaxall: It is particularly interesting that these studies have translated pathologic signaling mechanisms previously recognized to play a role in heart failure to the development of kidney disease. Therapies which inhibit GPCR-Gβγ signaling may prove efficacious in the prevention or treatment of both chronic and acute kidney damage in chronic heart failure patients, thereby improving survival and quality of life.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Dr. Blaxall:   Future work will further investigate the time of delivery of this therapy to offer the greatest level of protection to heart failure patients, along with whether this approach will apply to both pediatric and adult patients. The ultimate goal of these studies is to one day utilize this therapeutic approach for the treatment heart failure patients and those undergoing heart-lung bypass to prevent acute and chronic kidney injury.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

F. A. Kamal, J. G. Travers, A. E. Schafer, Q. Ma, P. Devarajan, B. C. Blaxall. G Protein-Coupled Receptor-G-Protein -Subunit Signaling Mediates Renal Dysfunction and Fibrosis in Heart Failure. Journal of the American Society of Nephrology, 2016; DOI: 10.1681/ASN.2015080852

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Last Updated on June 15, 2016 by Marie Benz MD FAAD