Cleveland Clinic team posts a big target for CKD drug developers

Stanley Hazen of the Cleveland Clinic--Courtesy Cleveland Clinic

Scientists at the Cleveland Clinic say that they have nailed down solid evidence that the gut metabolite trimethylamine N-oxide (TMAO) is directly responsible for chronic kidney disease. And aside from trying to develop a new dietary program, they're offering it up as a target for drug developers interested in pursuing the pathways involved in the disease.

The investigators say that the metabolite is formed through the digestion of egg-, red meat- or dairy-derived nutrients choline and carnitine. Their work was published in the Jan. 30 print edition of Circulation Research.

TMAO is already a likely culprit in heart disease. And after following thousands of CKD patients for 5 years the team says there is little doubt that CKD is another condition that you can tie to the metabolite.

"It's a triple whammy," said the Cleveland Clinic's Stanley Hazen. "Elevated plasma TMAO levels in subjects are linked to future cardiac risks, and in subjects with normal renal function, elevated levels predict long-term future risk for development of chronic kidney disease; animal model studies show that long-term exposure to higher levels of TMAO promotes renal functional impairment and atherosclerosis; and as the kidneys lose function, TMAO isn't eliminated as easily, and levels further rise, increasing cardiovascular and kidney disease risks further."

An estimated 20 million Americans suffer from CKD, many undiagnosed. But if left untreated the disease triggers a gradual loss in kidney function that can require an organ transplant or kill patients.

- here's the release

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