Three-year clinical trial finds reducing uric acid levels in type 1 diabetes provides no beneficial impact on the progression of diabetic kidney disease

BOSTON – (November 8, 2019) – Diabetic kidney disease (DKD) remains one of the most intractable complications of diabetes. Progress has been made using glycemic and blood pressure control, but the search continues for improved treatments for the estimated one in four adults with diabetes who has some level of nephropathy and continues at risk for eventual kidney failure.

Observational studies have shown that higher serum uric acid (SUA) is associated with a higher risk of DKD in type 1 diabetes. This held out the possibility that reducing blood levels of uric acid might prevent or slow the progression of the disease.

The Preventing Early Renal Loss in Diabetes (PERL) study was established in 2013 as a 16-site, multinational (US, Canada, and Denmark), randomized, placebo-controlled clinical trial to test whether sustained reductions of SUA would benefit patients’ kidney health. The conclusions of the study were announced today at the annual meeting of the American Society of Nephrology: three years of sustained reductions of blood levels of uric acid with the generic drug allopurinol did not benefit type 1 diabetes patients with mild to moderate kidney disease.

“On the one hand, we are disappointed because we don't have something new to offer to people with type 1 diabetes who are at risk for kidney problems,” says Alessandro Doria, MD, PhD, MPH, Senior Investigator in the Section on Genetics and Epidemiology, Professor of Medicine at Harvard Medical School, and co-principal investigator of the study with S. Michael Mauer, MD, University of Minnesota Medical School. “On the other hand, we are quite satisfied by the fact that we have provided a clear, unambiguous answer to an important scientific question.”

While the initial hypothesis was disproved, this study focused on a limited subset of the diabetes community. “We cannot exclude that in people with type 2 diabetes or with different stages of kidney disease, there might be an effect,” says Doria.

The research team plans to continue monitoring the PERL cohort, both to assess the possibility of delayed effects of allopurinol on the group and to gather more data on the development of diabetic kidney disease over time and on the risk factors. 

“We have an amazing biobank of samples that we collected during the study. And one can correlate biomarkers measured in those samples with long-term health outcomes. The longer the follow-up, the more power there is in the study because we’d have a longer snapshot of the trajectory of declining kidney function in these people.”

Alessandro Doria, MD, PhD, MPH
Senior Investigator in the Section on Genetics and Epidemiology

The PERL study was funded by grants from National Institutes of Health and JDRF.

Other institutions involved in the study included the University of Minnesota (Minneapolis), University of Colorado (Denver), University of Michigan (Ann Arbor), University of Toronto (Toronto), Northwestern University (Chicago), Albert Einstein College of Medicine (New York), Steno Diabetes Center (Copenhagen, Denmark), University of Washington (Seattle), University of Calgary (Calgary), University of Alberta (Edmonton), Emory University (Atlanta), Washington University (St. Louis), University of Texas Southwestern (Dallas), Providence Medical Research Center (Spokane), BC Diabetes (Vancouver).

Joslin Diabetes Center is world-renowned for its deep expertise in diabetes treatment and research. Joslin is dedicated to finding a cure for diabetes and ensuring that people with diabetes live long, healthy lives. We develop and disseminate innovative patient therapies and scientific discoveries throughout the world. Joslin is an independent, non-profit institution affiliated with Harvard Medical School, and one of only 16 NIH-designated Diabetes Research Centers in the U.S.

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