Injury to the kidney's tubular cells is one potential mechanism by which those metabolites might lead to kidney failure. "Many of the uremic solutes that were increased are handled by the tubules and are actively secreted by those cells," Niewczas says. The high levels of these metabolites might be a sign of tubular injury, and they might also contribute to this injury.
Additionally, the researchers found a strong correlation between higher concentrations of myo-inositol, a metabolite involved in insulin signaling and in many other biological processes, and progression to ESRD.
"Metabolomics is an exciting new field, and this exploratory study is rich in very robust findings," says Niewczas. "Until now, researchers generally were focusing their studies on uremic solutes just at the single-metabolite level, but here we used a very robust, high-throughput platform that screened a few thousand metabolites instead."
"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," she adds.
Earlier findings by the Krolewski lab may be already headed toward clinical diagnostic use. In 2012, researchers found that high concentrations of the proteins TNFR1 and TNFR2 in blood accurately predict the risk of kidney function loss in both type 1 and type 2 diabetes 10 years in advance. This work has been licensed to a firm that develops diagnostic tests, and a clinical test will be available in the near future, says Niewczas.
|Contact: Jeffrey Bright|
Joslin Diabetes Center