About 33% of people with type 2 diabetes suffer kidney damage that progresses to end-stage renal disease (ESRD). Scientists have thought that this kidney disease is driven by damage to the glomeruli, blood vessels in the kidney, which spill the protein albumin into the urine. However, a new study by Joslin Diabetes Center researchers that compares the metabolic fingerprints of patients who develop ESRD versus those who don’t has furnished new clues to the disease.
Published in Kidney International, the study examined the metabolism of patients while they were still healthy or in very early stages of the disease. The analysis drew on the Joslin Kidney Study, selecting 40 patients from that study who progressed to ESRD and 40 patients who remained alive without ESRD during eight to 12 years of follow-up. The Joslin researchers used global mass spectrometry to look for levels of approximately 2,400 metabolites (molecules produced during metabolism) in plasma samples from the patients.
Among the results, the scientists found 16 “uremic solute” molecules present in much higher levels in those who would go on to develop ESRD than those who would not develop the condition. Additionally, the researchers found a strong correlation between higher concentrations of myo-inositol, a metabolite involved in insulin signaling and other biological processes, and progression to ESRD.
“Metabolomics is an exciting new field, and this exploratory study is rich in very robust findings,” says lead author Monika Niewczas, MD, PhD. “Alterations of metabolism in general are key to diabetes, and studies like this may have huge potential for unraveling new pathways which will lead to developing new drugs and new diagnostic tests.”
