Diabetic Kidney Disease:
The Search for New Therapeutics
In Canada, diabetes affects an estimated 5.8 million people – about 15 per cent of the population. By the year 2034, that number is expected to rise to 7.3 million – approximately 16 per cent of the projected population.
Sadly, diabetes complications can reduce one’s lifespan by 5 to 15 years. People with diabetes often suffer from complications related to the kidneys, known as diabetic kidney disease (DKD). In fact, half of all kidney failures that require dialysis are attributed to diabetes and DKD.
DKD progresses slowly over many years, though it tends to progress more readily in men compared to women. With few treatment options, none of which halt prevention of the disease, it ultimately leads to end-stage kidney disease.
To tackle these health concerns, scientists from St. Joe’s Kidney research pillar have been searching for new therapies to improve kidney health in people living with diabetes.
Dr. Sergi Clotet-Freixas (pictured right) conducts research on the kidneys at the cellular level. An assistant professor in the Department of Medicine, Division of Nephrology at McMaster University, Dr. Clotet-Freixas joined the Hamilton Centre for Kidney Research (HCKR) at St. Joe’s in 2023 after completing a postdoctoral fellowship at University Health Network in Toronto.
In early 2024, his postdoctoral research on sex-based differences in kidney metabolism found in the blood of men and women with diabetes was published in the journal Science Translational Medicine. In this study, Dr. Clotet-Freixas and Dr. Ana Konvalinka identified a product of cellular metabolism called pyruvate that was found in higher concentrations in female kidney cells. He believes the discrepancy in pyruvate levels between men and women could explain why some women with diabetes are protected from DKD.
At the HCKR, Dr. Clotet-Freixas is now working to further understand underlying molecular changes that cause DKD in order to develop new treatment pathways.
Within the kidneys, lipids and glucose produce energy for the cells. Unfortunately, higher levels of glucose observed in diabetes have been shown to damage kidney cells. Moreover, kidney cells are not able to utilize lipids properly in the context of diabetes. Yet, scientists aren’t certain why diabetes causes injury to the kidney cells or how the disease alters their function, which highlights the importance of this work.
Dr. Clotet-Freixas and his research team have identified a protein that may control the improper use of lipids and glucose within kidney cells. The protein – called KDM6A – may also affect kidney cells’ predisposition to injury in diabetes.
In early 2025, Diabetes Canada awarded Dr. Clotet-Freixas with their End Diabetes Award, which will provide his lab with $450,000 in funding over three years. The funding will be used to explore the effects of removing KDM6A from kidney cells, which will help scientists determine whether the protein is a suitable target to develop novel therapeutics for treating DKD.
“Diabetes rates continue trending upward, which further emphasizes the importance of this work,” said Dr. Clotet-Freixas. “I’m grateful for the funding provided by Diabetes Canada and its donors, which will help us in the search for a novel, effective treatment.”
Thanks to this funding, Dr. Clotet-Freixas and his team now have data on thousands of genes that apparently are being controlled by KDM6A in kidney cells, many of which are related to lipid metabolism.
“This has generated a very important lead in our efforts to understand how KDM6A may be harmful for kidney cells in people affected by diabetes,” said Dr. Clotet-Freixas. “Maya Bozzo-Rey [pictured right], an exceptional graduate student in the lab, is working diligently to follow-up on these exciting findings.”
Scientists like Dr. Clotet-Freixas and his colleagues within the Hamilton Centre for Kidney Research continue to lead efforts to transform the management of health conditions related to diabetes.