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Researchers at Washington University School of Medicine in St. Louis noted that patients with chronic kidney disease (CKD) are at high risk of death from cardiovascular disease, and that recent studies have shown that a high level of phosphate in the blood is a major source of cardiovascular death risk in these patients.
In tests on mice with CKD, the researchers found that high blood phosphate levels directly stimulate calcification of blood vessels and that phosphate-binding drugs can decrease this vascular calcification. This means drugs that reduce phosphate levels may help protect CKD patients from cardiovascular disease, the researchers said.
The study was published in the Journal of the American Society of Nephrology.
"One of the kidney's functions is to help maintain a constant balance of phosphate in the bloodstream," senior author Dr. Keith A. Hruska, director of the Division of Pediatric Nephrology and professor of pediatrics, medicine and of cell biology and physiology, said in a prepared statement.
"When kidney failure occurs, an excess of serum phosphate develops. It turns out that high phosphate serves as a signal that stimulates cells within blood vessel walls to become bone-forming cells and to deposit calcium crystals. That produces vascular stiffness that is a cause of cardiovascular mortality," Hruska explained.
Based on the evidence from this and other studies, the U.S. Food and Drug Administration recently decided to extend the label of phosphate-binding drugs on the market. These drugs — calcium acetate (PhosLo), sevelamer (Renagel) and lanthanum carbonate (Fosrenol) — will now be labeled to indicate they are approved for treatment of high serum phosphate levels in CKD patients.
About 19 million Americans have chronic kidney disease.
Hruska and his colleagues also found that a growth factor called BMP-7 (bone morphogenic factor-7) reduced phosphate levels and calcification of blood vessels in mice with CKD.
"Elderly osteoporosis patients and people with diabetes have high rates of cardiovascular disease and high levels of vascular calcification. So, our findings may have importance even beyond patients with CKD," study co-author Dr. Suresh Mathew, an instructor in pediatrics, said in a prepared statement.
SOURCE: Washington University School of Medicine in St. Louis, news release, April 17, 2008
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