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Diabetes research ties inflammatory proteins with CKD progression
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Researchers at the Joslin Diabetes Center in Boston have identified circulating proteins that may be involved in the progression of diabetic kidney disease to ESKD.
In a study published in Nature Medicine, principal investigator Andrzej Krolewski, MD, PhD, head of the section on genetics and epidemiology at Joslin and professor of medicine at Harvard Medical School, and Monika Niewczas, MD, PhD, MPH, assistant investigator at Joslin and assistant professor of medicine at Harvard, along with other researchers identified a group of 17 circulating inflammatory proteins that are consistently associated with the development and progression of diabetic kidney disease, according to a press release from Joslin.
“Chronic inflammation is strongly implicated in the progression of [diabetic kidney disease] DKD, but the underlying mechanisms responsible for the inflammation are largely unknown,” the authors wrote. “Little consideration has been given to whether this process varies according to type of diabetes and stage of DKD. Previous studies examining the role of inflammation were mainly cross-sectional and focused on a few candidate inflammatory proteins and their association with kidney morphological lesions, the severity of albuminuria or the degree of impaired renal function.”
Tracking the 17 proteins, called the kidney risk inflammatory signature (KRIS), could allow physicians to determine the risk of progression to ESKD in a patient with diabetic kidney disease.
The Joslin researchers reviewed data from 219 patients with type 1 diabetes and 144 patients with type 2 diabetes and with kidney disease who had been monitored for 7 to 15 years by the Joslin Kidney Study. To see if their findings held true in different groups of people, they also included data and specimens from a cohort of 162 Pima Indians with type 2 diabetes, who had been similarly followed during a period of 10 to 15 years.
“The finding is amazing,” Krolewski said in the release. “It looks like inflammatory processes in the underlying progression to end-stage renal disease are similar across two diabetes types and differing race backgrounds. The disease process is homogenous.”
Researchers looked at each of the nearly 200 circulating inflammatory proteins using a SOMAscan platform.
“It was a comprehensive and unbiased evaluation on the role of almost all the known circulating inflammatory proteins, in contrary to what was done before where people were looking at a few candidate proteins,” Niewczas said. “What we found was that there are specific components of inflammation that are key drivers of the process, and this concept may have not been appreciated before.”
A follow-up mechanistic study is planned to help the researchers understand exactly what each protein does in the inflammatory process. Once these mechanisms are uncovered, the KRIS proteins could be therapeutic targets for drug developers.
Taken together, the findings reported in this paper suggest a new way to think about the progression of kidney disease, the researchers said.
“Our study has great potential to re-direct etiological studies on kidney complications in diabetes. Further exploration into the mechanisms could open up a whole new field of study,” Niewczas said in the release. “We hope that this will help to identify new therapies to prevent and treat diabetic kidney disease, one of the major causes of the development of ESRD in the U.S.”
Reference:
www.joslin.org/news/new-novel-circulating-proteins-involved-in-progression-of-diabetic-kidney-disease-to-end-stage-renal-failure.html
Disclosure: This research was supported by grants from the Juvenile Diabetes Research Foundation, the NIH, the Novo Nordisk Foundation and the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases.