Dr. Matthew Lanktree

Dr. Matthew Lanktree


Dr. Matthew Lanktree is a kidney doctor and scientist studying nephrology genetics, with special expertise in polycystic kidney disease, at St. Joseph’s Healthcare Hamilton and McMaster University. Dr. Lanktree is supported by the Canadian Institutes of Health Research, the Canadian and American Societies of Nephrology, the Kidney Foundation of Canada and “KRESCENT” the Canadian national kidney scientist training program. Dr. Lanktree has published over 60 articles in high impact journals in genetics and medicine. Dr. Lanktree has set his goal to use studies of our DNA to improve the care of patients with kidney disease.

Most Significant Research Contributions

  1. Uncommon genetic variants with allele frequencies less than 5% contribute to the distribution of complex traits with small and medium effect sizes. Rare mutations cause Mendelian monogenic diseases with extreme phenotypes. After collecting both patients with extreme phenotypes and genotypes from >100,000 participants from more than 50 studies, we obtained adequate power to identify uncommon genetic variants affecting complex traits such as height, body mass index, and triglycerides with modest effect sizes in genome-wide association studies (Nat Genet 2010:42:8:684-7, Am J Hum Genet 2010:88:1:6-18, Hum Mol Genet 2013:22:1:184-201).
  2. The prevalence of mutations causative of autosomal dominant polycystic kidney disease (ADPKD) are ~1 in 1000 in the general population, while truncating mutations in genes causative of autosomal dominant polycystic liver disease (ADPLD) are ~1 in 500. Using large databases of whole genome sequencing, I was able to support epidemiological estimates of the prevalence of ADPKD, and demonstrate that individually rare variants are cumulatively more common than previously suspected suggesting either incomplete penetrance or incomplete ascertainment of mild ADPKD (J Am Soc Neph 2018:29:10:2593-2600).
  3. At least 11% of families with ADPKD have extreme intrafamilial phenotype discordance and patients with severe ADPKD mutations may still have mild disease. Screening families in the extended Toronto Genetic Epidemiology Study of Polycystic Kidney Disease (eTGESP) identified 11% of families had members with aggressive disease and members with mild disease. Understanding the basis of intrafamilial variability, despite carrying the same disease causing mutation, will advance our understanding of ADPKD pathophysiology. Moreover, 21% of patients with severe protein truncating mutations had surprisingly mild disease (KI Reports 7:4(7):995-1003, submitted to J Am Soc Neph).
  4. Low high-density lipoprotein (HDL) cholesterol is a risk factor for chronic kidney disease (CKD). In one of the first large Mendelian randomization studies in Nephrology, we showed that a lifetime of genetically lowered HDL cholesterol was a risk factor for CKD, while elevated low-density lipoprotein cholesterol was not. HDL raising therapies have not been examined as a treatment for CKD (Am J Kid Dis 2018:71:2:166-172).
  5. Shifting to a precision medicine paradigm for the treatment of ADPKD. Incorporation of advanced imaging, biomarker and genetic testing, as well as patient preferences, forms a precision medicine approach to identify patients at greatest risk of kidney disease progression in ADPKD. Early treatment of asymptomatic patients with ADPKD is associated with a therapeutic burden, but slows cyst growth and delays subsequent loss of kidney function (Nat Rev Neph 2017:13:12:750-768, Neph Dial Transplant epub 2018, Can Med Assoc 2017:189:45:1396).