Grant: Operating Grant

Kidney disease caused by diabetes is the most common cause of kidney failure in Canada. To stop kidney disease developing or getting worse, people with diabetes are often given treatments that try and lower their blood sugar or control their blood pressure. While these treatments are helpful, kidney function continues to worsen in most people with diabetic kidney disease and new treatments are needed. The first sign of kidney damage in diabetes is the leaking of protein into the urine, which is often caused by damage to special cells in the kidney called podocytes. These podocytes form a barrier in the tiny filters of the kidney, known as glomeruli, but when the kidney is damaged this barrier can leak proteins into the urine. New treatments to keep podocytes healthy therefore have the potential to slow kidney damage in diabetes. JAK2 is a molecule present in many cells that has an important role in cell growth and survival. Recent studies have suggested that too much JAK2 could cause kidney damage in diabetes. In our initial exploratory studies we have discovered that JAK2 may lead to podocyte damage in diabetes. In these experiments we will explore how diabetes causes too much JAK2 in podocytes and how JAK2 may contribute to podocyte damage. We will look to see whether taking out the gene for JAK2 just from podocytes protects kidneys from damage due to diabetes and we will test to see if blocking JAK2 with new treatments prevents kidney failure in diabetes. If we show that doing this helps protect the kidney from damage it will provide important new information supporting the development of JAK2 inhibitors for diabetic kidney disease.