Urea buildup in kidney disease patients may cause diabetes

A team from the University of Montreal Hospital Research Centre (CRCHUM) has discovered a novel link between chronic kidney disease and diabetes.

The researchers highlighted the surprisingly toxic role of urea, a nitrogenous waste product normally filtered by the kidneys and excreted in urine. "In patients with chronic renal failure, the kidneys are no longer able to eliminate toxins,” said nephrologist Laetitia Koppe, a researcher on the study. “Urea is part of this cocktail of waste that accumulates in the blood. In nephrology textbooks, urea is presented as a harmless product. This study demonstrates the opposite, that urea is directly responsible for impaired insulin secretion in chronic kidney disease."

At the heart of pancreatic beta cells, researchers identified a particular protein, called phosphofruktokinase 1.

"The function of this protein is altered by an increase in blood urea, which occurs in chronic kidney disease. Increased urea causes impaired insulin secretion from the pancreatic beta cells. This creates oxidative stress and excessive glycosylation of phosphofructokinase 1, which causes an imbalance of blood glucose and may progress to diabetes," said Dr. Vincent Poitout, principal investigator of the study and professor at the University of Montreal and the Canada Research Chair in Diabetes and Pancreatic Beta-Cell Function.

The study is important because it reveals a link and rather novel mechanism between chronic kidney disease and diabetes. "Further studies are required to validate these findings in humans. But if our observations are confirmed, it will mean that patients with non-diabetic chronic kidney disease are at risk of developing diabetes. One might then suggest therapeutic approaches, such as taking antioxidants, which may protect pancreatic beta cells and reduce the risk of developing diabetes," said Poitout. -by Rebecca Zumoff