ELEVATE seed grants were awarded to (clockwise from top left): Drs. Gregory Hundemer, Ann Bugeja, Ayub Akbari, Deborah Zimmerman and Christopher Kennedy
The Ottawa Hospital’s Research Institute is awarding five ELEVATE seed grants to kickstart innovative kidney research projects.
The grants, worth a total of $200,000, focus on areas such as preventing kidney disease, enhancing access to kidney transplantation and improving care for transplant recipients. They were selected after a rigorous review by a panel of internal and external researchers as well as patient partners.
The inaugural ELEVATE competition, held in 2022, focused on early-career researchers, while the main 2023 competition focused on inflammation and the immune system. ELEVATE is funded in part through undesignated gifts to The Ottawa Hospital’s Research Institute through The Ottawa Hospital Foundation. A second ELEVATE stream for kidney research was added in 2023 as a way of broadening and strengthening a generous gift from a particular donor.
“Through our strategic planning process, we identified the need for a seed funding program to kickstart innovative projects and help researchers generate preliminary data for larger external grant applications,” said Dr. Duncan Stewart, Executive Vice-President of Research at The Ottawa Hospital and professor of medicine at the University of Ottawa. “We look forward to seeing the impact of these projects and funding further competitions in the future.”
Research project lay summaries:
Can AI improve dosing of kidney anti-rejection drugs?
Dr. Ayub Akbari Over 20,000 Canadians live with a kidney transplant, with rates of new transplants rising every year. A medication that suppresses the immune system called tacrolimus is often used to keep the body from rejecting the organ, but the dosing needs to be just right. Too low, and the kidney is rejected. Too high, and the kidneys or nervous system can be damaged. Alarmingly, less than half of patients achieve the ideal levels of tacrolimus in their blood during the critical three months after a transplant. This is partly because dosing strategies do not account for patient factors that can impact these drug levels. We will develop an AI-based tool to guide tacrolimus dosing. This has the potential to improve outcomes for kidney transplant patients by making dosing more accurate. To do this, we will use data from The Ottawa Hospital’s kidney transplant clinic, which performs over 100 transplants a year and is one of the largest in Canada.
Project team: Ayub Akbari (pictured) Greg Hundemer, Ran Klein, Christopher Mccudden, Cedric Edwards, Babak Rashidi, James Green, Martin Klamrowski, Elmira Amooei.
Are there sex differences in high blood pressure treatment and the development of kidney disease?
Dr. Ann BugejaUnmanaged high blood pressure can lead to chronic kidney disease by causing the blood vessels around the kidney to narrow, weaken or harden. This can be prevented by managing high blood pressure through healthy lifestyle and medication. There are biological differences in the development of high blood pressure in women and men and their kidney outcomes. However, there has been little research to see if men and women both receive evidence-based treatments when they are first diagnosed with high blood pressure. To find out, we will look at data from all men and women aged 66 and above diagnosed with high blood pressure in Ontario between Jan 2017-Dec 2021. We will look at what treatment they were first prescribed, and whether they went on to develop kidney disease. Our hypothesis is that women are less likely to receive evidence-based treatment for high blood pressure than men, resulting in worse kidney outcomes. This study is a vital first step in understanding sex disparities in high blood pressure treatment and kidney outcomes, which can help guide care and shape health policy for women’s kidney health in Canada.
Research team: Ann Bugeja (pictured), Manish Sood, Greg Hundemer, Greg Knoll, Marcel Ruzicka
Does mild primary aldosteronism impact the progression of kidney disease?
Dr. Gregory Hundemer One in ten adults live with chronic kidney disease (CKD), which increases their risk of cardiovascular disease and kidney failure. CKD progresses faster in some people than in others. One explanation could be primary aldosteronism (PA), a very common yet often unrecognized cause of high blood pressure. Caused by excess production of the hormone aldosterone, PA leads to higher rates of cardiovascular and kidney disease compared to other types of high blood pressure. Also, a growing body of evidence shows that milder forms called “Subclinical PA” are very common in the general population and often go undiagnosed. In this project, we will examine whether Subclinical PA explains why some patients with CKD have more rapid cardiovascular and kidney disease progression than others. If this is the case, our results could lay the foundation for future clinical trials that incorporate screening for PA into CKD management. The health consequences of PA are preventable with medications, so increased screening for it may be able to improve CKD patients’ long-term outcomes.
Research team: Gregory Hundemer (pictured), Manish Sood, Tim Ramsay, David Colantonio
Studying the kidney’s leaky filters in nephrotic syndrome
Dr. Christopher KennedyChildhood idiopathic nephrotic syndrome happens when the immune system damages important cells in the kidney’s filters called podocytes. These damaged podocytes let too much protein leak out of the blood and into the urine. Children with this syndrome are at increased risk of infection, cardiovascular disease and kidney disease. Their symptoms are treated with steroids and other medications, but there is no cure. One of the barriers to developing treatments is that there is no animal model of this syndrome’s podocyte damage that can be studied in the lab. We plan to fix that by developing a mouse model of this podocyte damage. This model will let us examine the cellular changes in the podocytes, and the molecular mechanisms behind how they are being injured. A better understanding of how this syndrome unfolds could hopefully one day lead to better treatments.
Research team: Christopher Kennedy (pictured), Dylan Burger (Co-Investigator), Robert Myette (MD/PhD student), Chet Holterman (Research Associate)
Are blood transfusions affecting kidney transplant success in Canada?
Dr. Deborah Zimmerman The body uses markers called HLA (human leukocyte antigens) to tell which cells belong to the body and which do not. After a blood transfusion, the immune system may produce antibodies to identify the foreign HLA markers in the body, a process called allosensitization. In patients with end stage kidney disease waiting for a kidney transplant, allosensitization has been linked to longer wait times due to fewer eligible donors and an increased chance of organ rejection. In the U.S., a study found over 80% of potential kidney transplant recipients needed a blood transfusion over a two-year period. It’s unclear if the same is true in Canada. To begin to find out, our team will look at data from all patients eligible for kidney transplants at The Ottawa Hospital between 2006 and 2023. We will determine the rate of blood transfusion and the impact of transfusion on allosensitization. This first step will be used to apply for additional funding to determine differences between blood transfusion practice in Ontario hospitals and the impact on allosensitization, to look at the importance of blood donor characteristics such as age and sex on allosensitization, and to provide an estimated sample size for a clinical trial to reduce the need for blood transfusions in this population.
Research Team: Deborah Zimmerman (pictured), Dean Fergusson, Alan Tinmouth, Johnathan Mack, Tim Ramsay.
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