Nov. 8, 2007 Kidney disease isn’t just about kidneys: Research has shown that people with kidney abnormalities have a dramatically increased risk of heart disease. But by studying blood samples from patients with early-stage kidney disease, researchers at The Rockefeller University Hospital hope to better define the connection.
A new pilot study, launched last month, involves adults diagnosed with kidney disease and focuses on a condition called endotoxemia, a buildup of toxins in the blood that may affect cardiovascular health. If the researchers’ hypothesis proves correct, the work will lead to follow-up studies to develop therapeutics.
Kidney disease has long been associated with a high incidence of atherosclerosis, or heart disease, but the reasons are not fully known. Certain conditions, including diabetes, high blood pressure and dyslipidemia, are often attendant with kidney disease and have been pinpointed as risk factors for atherosclerosis. “But the increase in risk for heart disease is larger than these traditional factors alone can account for,” says Manish Ponda, instructor in clinical investigation in Jan Breslow’s Laboratory of Biochemical Genetics and Metabolism and the study’s lead investigator.
To date, scientists have made a compelling case for endotoxins — natural breakdown products of bacteria — as a cause of atherosclerosis, and patients with end-stage renal failure commonly have high levels of endotoxins in their blood. However, this finding has not been well studied in early-stage kidney disease, which afflicts a much larger portion of the population.
What really convinces Ponda that there might be a causative link between kidney disease and endotoxemia is that even in early stages of kidney disease, patients exhibit characteristics that leave them vulnerable to developing endotoxemia, including a deficit of vitamin D and a “leakier” intestinal barrier — wider gaps between cells of the intestinal wall that usually protects against intruding bacteria.
The study, a collaborative effort between Rockefeller University and the Rogosin Institute, will analyze endotoxin levels in blood samples from men and postmenopausal women over the age of 50 who have early chronic kidney disease. “Kidney disease affects people of all ages, but narrowing our demographic helps to minimize age-related effects on endotoxemia and other risk factors,” Ponda says. In addition to endotoxin levels, the researchers will examine markers of inflammation and thrombosis, vitamin D levels and detailed lipid profiles.
“If the pilot study supports our hypothesis, we will proceed with interventional trials designed to reduce endotoxin levels in patients with chronic kidney disease,” Ponda says. “Kidney disease is a growing epidemic, affecting millions of Americans. Through our research we’re hoping to lessen its burden.”
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