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Feb 9, 2022

Study reveals ground-breaking approach to kidney disease prevention

Nephrology researchers at the University of Calgary are nearing the final stages of testing a potential world first in the treatment of acute kidney injury. The new therapeutic approach, which hinges on managing a tiny molecule that regulates inflammation in acute kidney injury and focuses on preventing the injury in people at risk of contracting the condition, such as those undergoing major cardiac surgery or a kidney transplant. 

“The hope is at least it improves the outcomes of acute kidney injury (AKI) because right now we have absolutely nothing to prevent it,” says Dr. Daniel A. Muruve, the senior researcher in a recent university study that looked at the importance of the molecule in the kidney and kidney-specific disease. The study, led by Dr. Arthur Lau of the Department of Medicine, Snyder Institute for Chronic Diseases, Cumming School of Medicine at the University of Calgary, was published last week in the international journal, Science Advances. Dr. Muruve, a Professor in Medicine and former Section Chief in the Division of Nephrology at the University of Calgary, says that even a 25 per cent improvement in the severity or incidence of AKI "would be a massive change to practice and to patient outcome.”

Commonly found in hospital settings where it occurs in up to two thirds of intensive care patients, acute kidney injury arises from tissue damage that can result when an interrupted blood supply returns to the kidney. Kidney organ transplantation, cardiac surgery, blood loss, and infection can all trigger the injury. AKI increases the risk of heart attacks, chronic or end-stage kidney disease, and death. Currently, there is no treatment of the condition once it occurs.

“AKI is a significant cause of chronic kidney disease, so having the opportunity to prevent its occurrence in the first place will have a considerable impact on the prevalence of kidney disease as a whole,” says Leanne Stalker, National Director of Research at The Kidney Foundation of Canada. The Foundation and the Canadian Institutes of Health Research (CIHR) were key funders of the study. The two organizations are also among several partners that founded the Kidney Research Scientist Core Education and National Training (KRESCENT) program that has supported the professional development of Dr. Justin Chun, one of the project researchers and an assistant professor in the University of Calgary's Department of Medicine.

Dr. Muruve says the molecule under study, called Dipeptidase-1, was discovered in the 1970s, but researchers — also from the University of Calgary — have only recently learned of the role it played in regulating inflammation in the lungs, liver, and kidneys. He likens the molecule’s job in inflammation to that of a police officer tasked with marshalling traffic. “It allows white blood cells, which are inflammatory cells, to attach to the kidney,” he explains.  

The study that was published last week explored the importance of this molecule in the kidney and for its role in specific kidney diseases., Researchers determined that by blocking the molecule’s activity in mice, they could prevent the inflammation that triggers AKI.

While the journey from research to accredited treatment often takes years or even decades, in this instance, researchers also found that at least two existing drugs successfully blocked the molecule’s performance in mice. “That’s what’s exciting,” says Dr. Muruve, who anticipates that clinical trials to test these drugs’ performance in people will begin within a year. 

The trials will focus on patients preparing for cardiac surgery, and Dr. Muruve says he anticipates The Kidney Foundation will help researchers collaborate with other institutions, disseminate information and recruitment for the study, and help to translate the knowledge garnered from the work back to the kidney community. 

Pat Taverner, a Calgary resident who contracted acute kidney injury following an operation to replace the aortic valve in her heart in 2015, says she thinks “it would be absolutely awesome, amazing, and life changing if there was a drug that they could have given me to prevent the failure of my kidneys.” 

Taverner spent three and a half years on dialysis before obtaining a kidney transplant. While life has been easier since the transplant, the 62-year-old notes she still must be careful to maintain her health. “I think the work being done is extremely important and valuable to prevent anyone else from having to go through what I did,” she says.  

Dr. Chun, who helped to conceive ideas, conduct experimental analysis, and revise the study’s manuscript, notes that the potential development in the treatment of AKI also highlights the importance of the KRESCENT program. He is currently a recipient of a three-year new investigator award under the program and was previously a recipient of a KRESCENT post-doctoral fellowship.

“A lot of funding and interest for basic science kidney research is dwindling and without the support of The Kidney Foundation of Canada and KRESCENT, we would have significantly reduced capacity to train and recruit people dedicated to basic science or translational kidney research,” Dr. Chun says. 

Such research is critical for supporting new directions to tackle kidney disease which often leads for the requirement for dialysis or organ transplantation. “There is a lot of hope to find new cures for kidney disease,” Dr. Chun says. “We need such programs to help foster future generations of kidney researchers. It’s crucially important, and there are too few of us right now.”

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