Mechanism Prevents Kidney Damage in Diabetics

Low levels of ACE (angiotensin-converting enzyme) and high levels of ACE2 may protect against kidney disease in the early stages of obesity-related diabetes. In the May issue of Hypertension, Daniel C. Batlle, MD, Earle, del Greco, and Levin Professor of Nephrology and professor of medicine at the Feinberg School, and colleagues describe a built-in biological mechanism that prevents kidney damage.

The researchers created a mouse model of Type 2, insulin-resistant diabetes to study the effects of ACE and ACE2. ACE is essential for the production of angiotensin II (Ang II), which causes blood vessel constriction and sodium and water retention in the kidneys and leads to kidney damage. ACE2 prevents the accumulation of Ang II and promotes formation of Ang(1-7), a substance that removes excess water and sodium from the kidneys. Mice with high blood glucose levels but no evidence of diabetes-related kidney disease had low levels of ACE and high levels of ACE2.

Dr. Batlle and colleagues noted that administration of ramipril—an ACE inhibitor commonly prescribed to treat high blood pressure and heart failure, improve survival after heart attack, and slow progression of kidney disease—resulted in the same pattern of low ACE levels accompanied by high levels of ACE2