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Thomas Mavrakanas, MD

Award:  KRESCENT New Investigator Award
Institution: McGill University
Year: 2023-2026

Study title: Novel therapeutic strategies in cardiorenal medicine

Biography
I am a nephrologist, clinician scientist, and assistant professor at McGill University.
I hold a Medical Diploma and a Master of Science degree in medical research methodology from the Aristotle University in Thessaloniki. I have completed my specialty training in (General) Internal Medicine in France and Switzerland and in nephrology at McGill. I also have an MD thesis in direct oral anticoagulants from the University of Geneva and a research fellowship from Brigham & Women’s Hospital, Harvard Medical School. I joined the McGill University Health Center nephrology division as assistant professor in December 2020.
 
My research has been focused on the causes of and treatments for cardiovascular disease in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). I have significant expertise in designing pharmacokinetic or cohort studies and using large datasets. I am also familiar with filing for regulatory approval of clinical trials. I am considered one of the world experts in direct oral anticoagulants in patients with CKD for my work on apixaban in ESRD. In addition, I was the first to describe the global burden of acute and chronic cardiorenal syndromes by presenting their association with all-cause mortality, myocardial infarction, and stroke.
 
I have 63 peer-reviewed publications and have received several competitive peer-reviewed grants or scholarships. My work has been published in the highest-ranking journals in Nephrology, including the Journal of the American Society of Nephrology, the Clinical Journal of the American Society of Nephrology, and the American Journal of Kidney Diseases.
 
I am currently working on treatment strategies to improve cardiovascular outcomes in patients with CKD and ESRD.
 
Lay Summary
Patients with kidney disease experience frequent complications from their heart or develop clots in their blood vessels. These complications are associated with significant disease burden or may lead to death. My research project is focused on understanding why these complications frequently occur in patients with reduced kidney function and how to optimally treat them. In my first project, we are dealing with patients who have kidney disease and are admitted to the hospital with difficulty to breathe because their heart cannot pump the blood out of their lungs. These patients need medications called diuretics to remove the water that has accumulated in their body due to poor heart and kidney function. However, it is not uncommon that diuretics may fail in removing the additional water that has been retained. In this project, we are studying a medication, called empagliflozin, in patients who fail to respond to diuretics. This drug belongs to a group of medication initially developed to treat diabetes, a condition associated with high blood sugar. We are assessing whether patients will produce more urine when they receive this drug in association with the treatment they are already receiving. This will be very important to help them get out of the hospital and avoid using an artificial kidney (procedure also known as dialysis).

In my second project, we are focusing on patients who suffer from a chronic decline in kidney function. These patients are getting heart disease more frequently or are having more serious heart disease, compared with patients with normal kidney function. In this study, we will be using a drug called canagliflozin. This drug also belongs to a group of medication initially developed to treat diabetes. However, it was shown that these drugs are also protecting the heart and the kidneys of patients who are receiving them. These drugs have not been widely used in patients with severely reduced kidney function. In addition, the right dose for these patients is not known. In this study, we would like to test whether giving this medication will reduce protein excretion in the urine, a common finding in patients with kidney disease. Reducing protein in the urine is protective for the kidneys and the heart. We hope that this project will help identify a better treatment for patients with severely reduced kidney function to protect their heart and kidneys. In my third project, we are studying the same medication for patients who have kidney failure and are receiving hemodialysis. We think that this drug may still protect the heart of patients whose kidneys have failed. However, this medication has never been studied in patients on hemodialysis. We will give canagliflozin to participants at the lowest available dose for nine days and verify that its levels in the blood are similar to drug levels in patients with preserved kidney function who are receiving the standard dose of the drug. Information on drug levels is important to establish safety if this medication is to be considered for a longer time period in a future study.

In the last project, we are interested in patients with nephrotic syndrome, a disorder associated with leaking of blood proteins in the urine. This condition sometimes has to be treated with an anticoagulant, i.e. a blood thinner, to prevent blood clotting. However, it is not known which specific conditions that cause nephrotic syndrome have to be treated with a blood thinner. We will measure the clotting properties of the blood at the beginning of the study and once the disease is adequately controlled with medical treatment. If the study demonstrates that blood tends to clot more while patients are still leaking protein in the urine and is back to normal when the disease is controlled, this may help change the way patients with nephrotic syndrome are managed.