Elevated levels of three circulating proteins have been found to help protect against kidney failure in diabetes, according to HMS researchers at Joslin Diabetes Center and their colleagues in industry and academia. The findings could provide biomarkers useful in detecting advancing kidney disease risk in people with diabetes and provide the basis for future therapies against the progression of end-stage renal disease, the most serious and advanced stage of diabetic kidney disease.
The investigators used high-throughput proteomic platforms to profile levels of slightly more than 1,000 proteins in plasma samples from a biobank of samples from patients who had been treated at Joslin. All samples were from patients with diabetes and moderately impaired kidney function. Samples were separated into two cohorts: individuals with type 1 diabetes and individuals with type 2 diabetes. The patients, most of whom were white, had been followed for between 7 and 15 years. The aim was to identify which proteins were elevated in individuals with slow or minimal decline in kidney function over the follow-up period.
The scientists found three proteins that were associated with protection against decline: fibroblast growth factor 20, angiopoietin-1, and tumor necrosis factor ligand superfamily member 12. Elevated levels of each protein were independently linked to a reduction of the odds of progressive kidney decline and progression toward end-stage renal disease. The combined effect of having elevated levels of all three proteins translated to very low risk for the severe disease.
The researchers are developing protocols for measuring levels of the protective proteins in clinical settings, hoping that the analyses will be used to identify patients at risk of progression to end-stage renal disease.
Md Dom ZI et al., Science Translational Medicine, June 2021