Grant: Operating Grant

Chronic kidney disease is a growing health care problem in Canada, and there are few treatments. Many kidney diseases eventually lead to the need for life-saving dialysis treatments or transplantation. Our laboratory is interested in finding the mechanisms causing kidney failure. With funding from the CIHR, we have studied the role of a protein called ACE2, which is produced in the kidney and may protect against kidney damage by removing a substance called angiotensin II. ACE2 also results in the formation of a substance called angiotensin-(1-7), which we found can block damaging effects of diabetes or angiotensin II on kidney tubular cells. We recently showed that blocking ACE2 in mice with kidney disease caused increased urinary loss of protein, which is a sign of worsening kidney damage. Furthermore, our preliminary data show that urinary ACE2 levels are high in people with kidney transplants, compared to people with normal kidneys. This suggests that in kidney disease, ACE2 may be released into the urine from the tubule, and its protective effects may be lost. In our grant to the CIHR, we will use a multi-disciplinary research approach involving a mouse model of kidney injury, isolated kidney cells and tubules, and studies in humans, to examine the potential protective effects of ACE2 in kidney disease. We will determine if ACE2 is shed into the urine in kidney disease, by a specific enzyme reaction in the tubular cell. We will also study the effect of loss of ACE2 on the development of kidney scarring, which is a feature of all chronic kidney diseases. Finally, we will learn more about angiotensin-(1-7) as a potential protective factor. Our research may lead to strategies to prevent the loss of ACE2 from kidney tubular cells in chronic kidney disease, which may improve kidney function. Our studies may also lead to new methods to identify people at risk for kidney disease progression, via measurement of urinary ACE2.