Enzyme May Hold Key To New Treatment Of Diabetic Kidney Disease

Armen Hareyan's picture

Diabetic Kidney Disease

Northwestern University Feinberg School of Medicine researchers have found that an enzyme called ACE2 may hold the potential to treat diabetic kidney disease, the most common form of kidney disease.

In the laboratory, researchers led by Daniel Batlle, professor of medicine in the Feinberg School, chief of the nephrology/hypertension division and staff nephrologist at Northwestern Memorial Hospital, have found low levels of the ACE2 enzyme in the glomeruli of the kidneys of diabetic mice. When ACE2 was further decreased with an inhibitor drug, kidney disease worsened. Studies are now needed using compounds that increase the level of ACE2 in the kidneys of diabetic mice to see if it reverses or prevents kidney disease from developing, Batlle said.


The experiments appear in a report by Ye et. al in the November issue of the Journal of the American Society of Nephrology.

Diabetes, which affects 230 million people worldwide and 21 million in the United States, is the leading cause of kidney failure. About one-third of patients with diabetes will go on to develop kidney disease. In diabetes, the small blood vessels in the kidneys are injured and the kidneys cannot clean the blood properly. In 2002, a total of 153,000 people in the U.S. with kidney failure due to diabetes were living on chronic dialysis or with a kidney transplant.

ACE inhibitors are currently used to treat kidney disease, said Batlle, the Earle, del Greco, and Levin Professor of Nephrology/Hypertension. "An eventual ACE2 therapy, perhaps combined with ACE inhibitors could be doubly effective," he said.

"This is a new frontier," said Batlle. "Targeting the ACE2 enzyme may be important, much in the same way as the introduction of ACE inhibitors two decades ago to treat high blood pressure and slow the progression of kidney disease."

In an editorial that accompanies the publication by Ye et al., Dr. Julie Ingelfinger writes, "The most important aspect of the Ye et al. report is that the work assessed the effect of an ACE2 antagonist, with or without an angiotensin receptor blocker. The ACE2 increased urinary albumin excretion in diabetic animals, but not in control animals. What of ACE2 and the development of therapies? In their article, Ye et al. suggest that ACE2 may regulate the levels of Ang- II within the glomulerulus by degrading it to Ang 1-7, a suggestion supported by the known actions of the enzyme. Such actions provide a rationale for embarking on strategies that might increase ACE2 in diabetes."