New target for treating prediabetes in patients with kidney disease

December 20, 2012

Insulin resistance, or , in individuals with kidney disease may be caused by the progressive retention of certain compounds that are normally excreted by the kidneys in healthy individuals, according to a study appearing in an upcoming issue of the Journal of the American Society of Nephrology (JASN). The findings might be used to prevent insulin resistance in kidney disease patients, which could lower their risk of developing .

Cardiovascular disease is the number one killer of patients with (CKD), and insulin resistance—a lowered level of response to insulin circulating in the blood—is an important cardiovascular risk factor in these patients. It's not clear why patients with CKD often develop insulin resistance, but the retention of compounds that are normally removed from the blood and excreted in the urine may play a role. One such compound is p-cresyl sulfate (PCS), a toxin that is produced by . PCS is retained in CKD patients, and it is poorly removed by most dialysis techniques.

Christophe Soulage, PhD, Denis Fouque, MD, PhD, and Laetitia Koppe, MD ( & Université de Lyon, in Villeurbanne, France) led a team that sought to determine whether PCS contributes to CKD-associated insulin resistance. They found that administering PCS to mice with normal kidney function for four weeks triggered insulin resistance, loss of fat mass, and a redistribution of lipids in the muscles and liver, mimicking features associated with CKD.

The researchers also found that mice treated with PCS exhibited altered insulin signaling in skeletal muscles. In addition, when mice with CKD were treated with a that reduces blood levels of PCS, insulin resistance and lipid abnormalities were prevented.

Taken together, these findings suggest that PCS contributes to insulin resistance and that targeting PCS may help improve the health of patients with CKD.

"Because is an important , novel therapeutic approaches like prebiotics that could decrease PCS more substantially than currently available strategies must be developed, especially since this toxin is not very efficiently removed by dialysis," said Dr. Soulage.

Explore further: Chronic kidney disease a recipe for kidney failure? Not necessarily

More information: The article, entitled "p-Cresyl sulfate promotes insulin resistance associated with CKD," will appear online at on December 20, 2012.

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not rated yet Dec 20, 2012
It is good to see American nephrology catching up with the rest of the world. The first year mortality for dialysis patients is about 22% in the US versus about 9% for other industrialized nations such as Japan and Italy, even though the US outspends all these nations.

Contrary to what this title suggests, the study of aromatic compounds produced by bacteria which is then absorbed and processed into toxins is not "new", the Japanese has been studying this for more than 20 years. In fact they have a drug called Kremezin or AST-120 that they have been giving CKD patients since the 1990s. It is effective in reducing the absorption of these aromatic compounds and effectively prevents the build up of several toxins in the CKD patients. Unfortunately, the US never adopted this very inexpensive active carbon based drug and it is still held up even after the recent phase 3 trials. It is perfectly safe, even if you do not have CKD, you can take it without harm.

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