Newly discovered proteins protect against the progression of diabetic kidney disease

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Elevated levels of three specific circulating proteins are associated with protection against kidney failure in diabetes, according to research from the Joslin Diabetes Center to be published June 30 in Scientific translational medicine.

“In addition to acting as biomarkers to advance the risk of kidney disease in , proteins may also serve as a basis for future therapies against progression to more severe types of kidney disease, “said Andrzej S. Krolewski MD, Ph.D., lead author of the publication, senior researcher at the Joslin Diabetes Center and professor of medicine at Harvard Medical School, which would likely include the delay and prevention of end-stage renal disease (ESRD), which is the most severe and advanced stage of diabetic kidney disease.

The study marks a step toward finding markers associated with protection against individual risk rather than an individual increase for the rapid progression of diabetic kidney disease. This should more directly lead to potential goals to slow progression, as it is based on the thought that individuals with slow progression will have some sort of protective factor.

“Our research has become possible recently,” Dr. Krolewski said. “We were able to look for these markers through the development of high-performance proteomic platforms. More importantly, the availability of biobank specimens we established many years ago in the Joslin kidney study was critical.”

According to the report, the researchers defined the levels of just over 1000 proteins in the plasma samples that were taken at the beginning of the original study. They all had diabetes and a moderate impairment of kidney function. They used two cohorts of individuals with type 1 or type 2 diabetes who were followed for 7 to 15 years.

The main goal was to identify elevated proteins in individuals with slow or minimal decrease in renal function during the follow-up period. It should be noted that they validated the initial results in another cohort of individuals with type 1 diabetes.

Newly discovered proteins protect against the progression of diabetic kidney disease

The cumulative incidence of end-stage renal disease (ESRD) according to the protection index of three proteins, Index = 0/3 does not indicate protection while Index = 3/3 indicates complete protection. Credit: Copyright Joslin Diabetes Center

Working through possible candidate proteins, they found three proteins that appeared to offer protection against progressive decline. These included fibroblast growth factor 20 (FGF20), angiopoietin-1 (ANGPT1), and tumor necrosis factor 12 ligand superfamily member (TNFSF12).

In each case, elevated circulating levels reduced the probabilities of progressive renal decline and progression to ERD. The combined effect of having high levels of the three proteins translates into a very low risk of ESRD.

“The protective effects of these proteins appear to be independent, suggesting that several mechanisms are involved. They may be causally related to the disease process or represent as yet unidentified pathways involved in progressive renal decline,” said Zaipul Md Dom , first author Ph.D., researcher in the laboratory of Dr. Krolewski

The authors go further to examine current biological knowledge related to individual proteins and kidney disease, identifying a number of possible mechanisms that could explain their protective effects. According to Dr. Krolewski, these are possible new research routes to follow.

Dr. Kevin Duffin, co-author of the publication, and to Eli Lilly, Diabetes and Diabetic Complications, said: “Our study identified specific circulating proteins that were depleted in patients with diabetes disease that evolved into ESRD. These results suggest that a personalized approach to medicine for the treatment of patients with low levels of protective proteins might be possible. We think we manage therapeutic mimetics or treatments that improve circulating levels of these depleted proteins may be the future. ”

Dr. Krolewski added: “We have already begun to develop protocols on how to measure the concentrations of protective proteins in clinical settings. We hope that these proteins can be used to identify patients at risk of progression to ESRD, who can then be treated with new therapies. “.


Researchers find new proteins in circulation that are involved in the progression of DKD to ESRD


More information:
ZI Md Dom et al., “Circulating proteins protect against renal decline and progression to end-stage renal disease in patients with diabetes.” Scientific translational medicine (2021). stm.sciencemag.org/lookup/doi/ … scitranslmed.abd2699

Citation: Recently Discovered Proteins Protect Against Progression of Diabetic Kidney Disease (2021, June 30) Retrieved June 30, 2021 at https://medicalxpress.com/news/2021-06-newly-proteins-diabetic-kidney -disease.html

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