End-Stage Kidney Disease: A Possible Biomarker of 10-Year Risk—and Therapeutic Target—for People with T1D

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In the United States, diabetic kidney disease, or DKD, is responsible for more than half of all new cases of end-stage renal (kidney) disease. What’s more, over the last few decades we saw improvements in all major diabetic complications, but end-stage kidney disease rates declined the least, and it is still a cause of premature death from diabetes.

There has been little in terms of biomarkers to tell who will get end-stage kidney disease. In 2012, researchers at the Joslin Diabetes Center, including Monika A. Niewczas, M.D., Ph.D., M.P.H., and Andrzej S. Krolewski, M.D., Ph.D., uncovered two protein markers that, when elevated in the blood, can predict the risk of kidney function failure in diabetes. Now, Dr. Niewczas, with a JDRF Career Development Award, and Dr. Krolewski go globally, to find all of the circulating inflammatory proteins that are associated with progression of the kidney disease in diabetes within 10 years of the observation.

In a publication in Nature Medicine, Dr. Niewczas, Dr. Krolewski and their team found 17 inflammatory proteins that were extremely robustly associated with progression for end-stage kidney disease—adding 15 more to their previous discovery. What’s more, these proteins were independent of blood-sugar control, suggesting that the effect of blood-sugar management is indirect and probably happens earlier in the disease course.

“Our comprehensive study unravels formerly underappreciated systemic drivers of diabetic kidney disease,” tells Dr. Niewczas. “Further, many of these proteins have never been considered before when researchers used focused approaches.”

If these proteins are involved in the progression of kidney function loss, could targeting these molecules and the involved inflammatory pathways lead to the prevention of end-stage kidney disease? Interestingly, many of the proteins are currently being tested in clinical trials for other chronic inflammatory disorders, including rheumatoid arthritis, inflammatory bowel disease and others. Further testing these compounds in diabetic kidney disease may offer hope to people living with T1D that they may thwart end-stage kidney disease altogether.

“These exciting findings broaden our understanding of how circulating inflammatory proteins contribute to diabetic kidney disease and highlight their importance as drug targets,” says Marlon Pragnell, Ph.D., lead of the JDRF Complications Program. “As these proteins circulate throughout the body, it’s intriguing to speculate that drugs targeting these in people with diabetes might also benefit other organs in addition to the kidney.”

The JDRF-funded investigators on the publication, now or in the past, include Drs. Niewczas and Krolewski, and Alessandro Doria, M.D., Ph.D., M.P.H., Paolo Fiorina, M.D., Ph.D., Matthias Kretzler, M.D., Jennifer Sun, M.D., M.P.H., and Katalin Susztak, M.D., Ph.D.

You are helping us find ways prevent, treat and—one day—cure T1D. To learn what JDRF is doing in complications research, go here.

By Alexandra Mulvey