24
June
2020
|
15:00
America/Tegucigalpa

Promising treatment to slow kidney disease doesn’t prove out in clinical trial

Reducing levels of uric acid in the blood doesn’t guard against complication in patients with Type 1 diabetes, researchers find.

By FOLIO STAFF

A drug that showed promise in slowing kidney disease in people with Type 1 diabetes has no clinical benefit for patients, according to results from a three-year clinical trial published today in the New England Journal of Medicine.

“This is not the result that we wanted,” said Peter Senior, a professor of medicine at the University of Alberta who was involved in the international study, “but it does give a very clear answer to an important scientific question.” 

 

Half or more of people with Type 1 diabetes develop kidney disease, which often progresses to kidney failure requiring hemodialysis or a kidney transplant for survival. This high rate has dropped slightly in recent years with the advent of better ways to control blood sugar levels and improved blood pressure drugs, “but diabetic kidney disease is still a huge problem,” said Senior.

Progression of kidney disease in Type 1 diabetes is correlated with increased amounts of a compound in the blood called uric acid. Hoping that a drug that reduces these uric acid levels would slow the disease, Senior collaborated with a network of investigators across North America and Denmark to conduct the Preventing Early Renal Loss in Diabetes (PERL) trial, which enrolled 530 participants with Type 1 diabetes and early to moderate kidney disease. 

The PERL trial grew out of several studies showing that people with higher levels of uric acid in their blood were more likely to display a high rate of kidney function loss. 

“This provided a clear reason to ask whether allopurinol—a drug that’s been on the market since the 1960s to reduce uric acid levels in gout—might be able to prevent this decline in kidney function,” said Senior, who is also a member of the Alberta Diabetes Institute

Participants in the three-year, placebo-controlled and double-blind trial received the current standard of care, including a renin-angiotensin system inhibitor—an existing type of drug shown in the 1990s to slow kidney damage, although incompletely.

The key measurement of kidney function for patients in the trial was glomerular filtration rate (GFR), a measure of how much blood is filtered every minute by the kidneys. GFR drops as kidney disease progresses. 

Over the three years of the study, levels of uric acid dropped about 35 per cent on average among people given allopurinol compared with those who weren’t. 

“But despite this very nice reduction in uric acid, we could not see any effect on GFR,” Senior said.

A second study from Australia on patients with a variety of chronic kidney diseases, some with diabetes, published alongside the PERL study, showed similar results.

Senior said he and his colleagues will continue to follow participants through their medical records and through national databases that track people who eventually progress to dialysis or kidney transplants.

Despite its disappointing conclusion, “PERL was a textbook example of taking clinical observations and preliminary research findings suggesting the potential for a new use for an old drug, and then designing a study to definitively answer whether or not the drug would prove to be effective as a new treatment,” Senior noted. 

“In this case, the drug did not show any of the anticipated benefit. But that is exactly why we do clinical trials, and how our scientific understanding advances. We don’t want to recommend treatments because ‘in theory’ they should work.”

The study was led by Antonio Doria of the Joslin Clinic in Boston and Michael Mauer of the University of Minnesota, with support from the U.S. National Institute of Diabetes and Digestive and Kidney Diseases and the Juvenile Diabetes Research Foundation.