Research Awards Recipients

Background: Polycystic kidney disease (PKD) affects approximately 1 in 1000 people, and 70% develop kidney failure by age 70. Therapies for PKD attempt to maintain kidney function and slow progression towards kidney failure, which requires kidney replacement therapy with dialysis or kidney transplantation. Patients at highest risk of early kidney failure have the most to gain from initiation of aggressive therapy and knowing a patient's risk of progression is important if we are testing the effectiveness of new treatments. Large kidney size, presence of an identified genetic mutation, and clinical risk factors such as high blood pressure, blood in the urine, or urine infections can help identify patients at highest risk of kidney failure. However, large studies including all of these risk factors have not been performed. Furthermore, examination of proteins found in the urine has been suggested to provide additional clues to PKD severity.

Hypothesis: By developing a comprehensive test including imaging, genetic testing, clinical risk factors, and urine protein analysis, we will learn more about PKD biology and improve our ability to identify patients at the highest risk of progression to kidney failure.

Methods: The Centre for Innovative Management in Polycystic Kidney Disease (CIMPKD) at University Health Network's Toronto General Hospital and University of Toronto has collected DNA, urine, and cyst fluid from over 2000 patients with PKD. Using cutting-edge magnetic resonance imaging (MRI), genetic testing using "next generation" sequencing, and urine protein analysis with mass spectrometry, coupled with the latest statistical and computational learning analysis techniques we will search for predictors of PKD severity. Findings will then be verified in other collections of PKD patients from collaborators around the world.

Clinical Significance: Incorporating imaging, genetics, clinical risk factors, and urine protein analysis will improve our ability to identify PKD patients at highest risk of kidney failure. Patients need this prognosis, as they may benefit from early aggressive therapy and enrollment in clinical trials of new treatments. Kidney failure is one of the most expensive conditions to treat in modern medicine, and each year without the need for dialysis leads to large cost savings and improvement in quality of life. Additionally, using genetic and molecular tests of urine and kidney cyst fluid, and “big data” from international collaborations, this research could lead to the identification of new treatments and possibly a cure for polycystic kidney disease.

Biography
Dr. Matthew Lanktree began research training during an undergraduate degree in bioinformatics at University of Waterloo, then completed a combined MD/PhD degree at University of Western Ontario studying complex disease genetics. Moving to McMaster University, he completed an Internal Medicine residency and a clinical fellowship in Nephrology before moving to University of Toronto to pursue a postdoctoral research fellowship in heritable kidney diseases, including polycystic kidney disease. Dr. Lanktree has received funding from the Canadian Institutes of Health Research and the American Society of Nephrology, and is a member of the Canadian Kidney Foundation KRESCENT program. Over the last 15 years, Dr. Lanktree has published over 50 articles in high impact journals in genetics and medicine, and has set his goal to improve outcomes for patients with polycystic kidney disease.