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A byproduct of intestinal bacteria may promote heart disease in kidney disease patients

July 30, 2015

By Donna Peck

Alan Yu and Jason Stubbs

New research by a team at the University of Kansas Medical Center finds that an organic byproduct of intestinal bacteria may contribute to cholesterol plaque (atherosclerosis) formation in the arteries of many patients with chronic kidney disease. Heart disease is the leading cause of death for people with kidney disease. The study, led by Jason Stubbs, M.D., an associate professor of nephrology at KU Medical Center, was just published in the Journal of the American Society of Nephrology.

Stubbs said the research focused on trimethylamine-N-oxide (TMAO), an organic compound that is generated following the metabolism of several dietary nutrients by certain intestinal bacteria. Research has shown that giving TMAO to rodents promotes atherosclerosis, and that humans with higher concentrations of TMAO in the bloodstream are at increased risk of developing heart disease.

"Since TMAO is primarily cleared from the bloodstream by the kidneys, we hypothesized that patients with reduced kidney function would demonstrate higher circulating levels of TMAO and subsequently, a higher incidence of heart disease," Stubbs said.

In a study of 104 patients with chronic kidney disease, Stubbs, along with Alan Yu, MB, BChir, director of the Kidney Institute at KU Medical Center, and their research team, found that blood levels of TMAO increased as kidney function declined. In a subset of six patients who underwent kidney transplantation, the procedure led to a significant drop in TMAO levels. Furthermore, in a separate group of 220 patients with chronic kidney disease, high levels of TMAO in the bloodstream were linked with an increased risk of atherosclerosis formation in the coronary arteries, as well as death over a four-year period. 

"This research could have an impact on millions of Americans," said Yu. "About 12 percent of adults in the United States, or 20 million people, have some form of chronic kidney disease. Of that population, 10 times more patients will die of heart or vascular disease than will end up progressing to end-stage kidney disease and require chronic dialysis therapy."

Although the study found that patients who had undergone kidney transplants had much lower levels of TMAO, transplants are not an option for most patients with chronic kidney disease. Stubbs said he is looking at other ways to lower TMAO in kidney patients.

"The solution will be much more complex than simply eliminating all intestinal microbes, because many intestinal bacteria play an essential role in maintaining overall health," Stubbs said. "But we are exploring how antibiotics and probiotics may be able to target and suppress particular bacteria that produce TMAO."

Stubbs said there is also research being conducted that is studying whether certain foods or a particular diet might produce less TMAO in the body.

Last modified: Jul 26, 2018
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