Study Reveals How Chronic Kidney Disease Can Cause Diabetes

Work at the University of Montreal shows how a urea impacts a protein, disrupting insulin secretion and elevating blood glucose.

Chronic kidney disease (CKD) is often thought of as a complication of diabetes, but CKD can also cause it, according to a new study from Canada.

Researchers at the University of Montreal Hospital Research Center uncovered the mechanism that can cause non-diabetic kidney disease to ultimately trigger diabetes, which is reported in the Journal of Clinical Investigation.

According to Vincent Poitout, DVM, PhD, director of the research center, observations with mice and humans have revealed how the inability to process urea causes toxins to build up in the body, impairing insulin secretion and elevating blood glucose.

In CKD, the kidneys slowly lose their ability to filter waste from the blood. As the disease progresses, patients must undergo dialysis or receive a kidney transplant. It often follows years of progression of diabetes, but researchers wanted to know why those who did not have diabetes at the start ultimately experienced elevated blood glucose levels.

Urea, which is normally excreted in the urine plays a surprising role in the process. “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," said Laetitia Koppe, MD, PhD, lead author on the paper.

The authors report that a protein in pancreatic beta cells, called phosphofruktokinase 1, is adversely affected by increased blood urea. The presence of the waste product impaired insulin secretion, causing oxidative stress and excessive glycosylation of the phosphofruktokinase 1. This, Poitout said, “causes an imbalance of blood glucose and may progress to diabetes.”

Uncovering this link could lead to a therapeutic solution, such as taking antioxidants to protect the pancreatic beta cells, he said. More studies are needed to confirm the findings in humans.

Reference:

Koppe L, Nyam E, Vivot K, et al. Urea impairs β cell glycolysis and insulin secretion in chronic kidney disease. Journal of Clinical Investigation, 2016; DOI: 10.1172/JCI86181