UT Southwestern evaluates allopurinol drug to prevent nephropathy in Type I diabetes patients

UT Southwestern Medical Center has joined an international clinical trial studying whether a drug traditionally used to treat gout can help prevent kidney damage in patients with Type 1 diabetes.

Researchers in the Preventing Early Renal Loss in Diabetes (PERL) clinical trial are evaluating the drug allopurinol in patients who have nephropathy, an early-stage kidney disease that is a frequent complication of Type 1 diabetes.

"Diabetes-related nephropathy is the No. 1 reason for dialysis in the United States and new approaches are needed to prevent progression of the disease. The current standard of care is useful, but clearly not enough. We can do better," said Dr. Ildiko Lingvay, Associate Professor of Internal Medicine, Division of Endocrinology, and Clinical Sciences at UT Southwestern.

The objective of the National Institutes of Health (NIH)-funded study is to determine whether lowering serum uric acid by means of allopurinol early in the course of kidney disease may be effective in preventing or slowing the decline of renal function in Type I diabetes patients.

Approximately 38 percent of people with diabetes will develop nephropathy, which is more common in Type 1 diabetics than Type 2 diabetics, according to the National Kidney Foundation. Diabetes is the leading cause of kidney failure in the U.S. and the seventh leading cause of death in the U.S, according to the Centers for Disease Control and Prevention. An estimated 1.25 million Americans currently live with Type 1 diabetes, with about 40,000 Americans diagnosed each year, according to the JDRF, a leading global organization focused on Type 1 diabetes research.

James Drake developed Type 1 diabetes when he was 22. Mr. Drake, now 53, had to give up his passion of traveling as a roadie with various bands due to complications that are now affecting his eyes and kidneys.

"It's hard to face life when you can't do what you want to do. My eyesight got bad because of my diabetes. I can't travel. I'm on disability now. I had to give up so many things," he said.

Much has changed about diabetes treatments since he was first diagnosed, and he said he was eager to contribute further to developing new treatments by participating in the PERL trial.

"I never imagined that there would be insulin pumps," he said. "I thought it was pretty cool that I was asked to do something that could lead to important improvements in care down the road."

A small pilot study using allopurinol showed promising results, and the study has now expanded to a large-scale, clinical trial with 14 sites, including two in Canada, one in Europe, and 11 across the U.S. UT Southwestern is the only site in Texas.

"The preliminary work that led to this study examined large databases for factors that were predictors for progression of nephropathy," said Dr. Lingvay, Endocrinology Fellowship Program Director. "Regardless of the models used or the risk factors evaluated, the level of uric acid always seemed to be a strong predictor of nephropathy. The higher the uric acid levels, the more likely it was that the nephropathy was progressing, hence the idea of using allopurinol, which lowers uric acid levels."

Allopurinol belongs to a class of medications called xanthine oxidase inhibitors. The drug is traditionally used to treat gout, kidney stones, and high levels of uric acid in the body caused by certain cancer medications, according to the NIH's National Library of Medicine. Allopurinol prevents the build-up of uric acid in the body.

Study participants are enrolled for three years and treated for nephropathy with an angiotensin receptor blocker or an angiotensin converting enzyme (ACE) inhibitor - the standard-of-care drugs for this condition - as well as either the allopurinol or a placebo.

"What's nice about this study is that we are repurposing an old drug that is cheap and has a demonstrated safety record," said Dr. Lingvay, who received an NIH Career Development Award.