The Kidney Foundation of Canada

Dr. Kevin Burns 

Dr. Kevin Burns

Ottawa Hospital Research Institute, Ontario

Exosomal transfer of MicroRNA-486-5p in acute kidney injury repair


2017-2019:  $100,000  |  Biomedical Research Grants  |  Category: Renal Failure

Biography

Kevin D. Burns, MD, FRCP(C) is Professor of Medicine in the Division of Nephrology and Vice-Chair for Research in the Dept. of Medicine at the Ottawa Hospital and the University of Ottawa. He is Senior Scientist and Director of the Kidney Research Centre of the Ottawa Health Research Institute, University of Ottawa, and is cross-appointed to the Department of Cellular and Molecular Medicine. Dr. Burns received his B.Sc. and M.D., C.M. from McGill University, and completed Internal Medicine Residency at the University of Ottawa. Following a clinical fellowship year in Nephrology in Ottawa, he undertook basic science research training at Vanderbilt University Medical Center. In 1992, he was awarded a 5-year Scholarship from the Medical Research Council of Canada, and he returned to Ottawa as a clinician-scientist. His research program has been supported by funds from the Canadian Institutes of Health Research (CIHR), the Kidney Foundation of Canada (KFOC), and the Canada Foundation for Innovation/Ontario Innovation Trust.

Dr. Burns was University and Hospital Division Head of Nephrology from 1997-2005. He is Past President of the Canadian Society of Nephrology (CSN) (2004-2006), and is Chair of the Steering Committee for the KRESCENT Program. Dr. Burns’ research is focused on the function and regulation of the intrarenal renin-angiotensin system, as this system pertains to the pathogenesis of kidney diseases, including diabetic nephropathy and hypertension. His laboratory uses a variety of methods in cell and molecular biology, as well as animal models of kidney disease. Dr. Burns is also involved in clinical research studies that aim to transfer knowledge from the laboratory bench to the patient’s bedside.

Lay Summary

Acute kidney injury (AKI) is a serious condition in which kidney function declines rapidly, often over minutes to hours. Therapy often involves use of dialysis, with the hope that the kidneys will eventually recover their function, although this occurs in only about one half of patients. Unfortunately, there are no treatments to accelerate the repair of injured kidneys after AKI.

Use of stem cells has been proposed to help injured kidneys recover their function. Recently, we isolated different “progenitor” cells from human umbilical cord blood and infused them into mice with AKI, induced by temporary blockage of blood supply to the kidneys. We found that one population of cells protected the mice from kidney injury. Furthermore, the cells themselves did not incorporate into the injured kidneys, but rather released factors that appeared to stimulate healing. In this regard, the cells shed tiny membrane particles (“exosomes”) that are enriched in a substance called “miR-486-5p”. Injection of mice with the exosomes strongly protects them from kidney injury, and the benefits appear to be at least partly due to transfer of miR-486-5p to the kidney.

Using exosomes to treat humans with AKI represents an exciting long-term research goal. Indeed, exosomes may offer distinct advantages over cell treatments, including a low risk of immune “rejection”, reduced chance of abnormal cell growth, and less potential to cause blockage of blood vessels due to their small size. However, a number of questions remain to be answered before studies can be conducted in humans. How can we optimize the delivery of exosomes to the kidneys after AKI, and do infused exosomes target specific kidney cells to promote repair? What is the effect of transfer of miR-486-5p in the protective response associated with exosome use after kidney injury, and what role does prevention of cell death play? What other molecular pathways in the kidney are affected by exosomes and miR-486-5p? In this grant, we will conduct animal studies to address each of these key questions. Our proposal represents the critical next step in developing new treatments for humans with AKI.