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Gene implicated in chronic kidney disease

Durham, N.C. -- Duke University Medical Center researchers have discovered a gene responsible for one form of chronic kidney disease. The disease, called familial focal segmental glomerulosclerosis (FSGS), can lead to complete kidney failure and affects 20 percent of patients on dialysis. The finding could lead to more effective treatments, according to the researchers.

By examining the genetic makeup of one large, multi-generational family with a dominant form of FSGS, the researchers linked a mutant form of the gene called Transient Receptor Potential Cation Channel 6 (TRPC6) to the disease. What's more, because the gene differs in function from those earlier implicated in FSGS, the finding represents a novel mechanism of kidney damage, said Michelle Winn, M.D., a kidney specialist and geneticist at the Duke Center for Human Genetics and lead author of the study.

Drugs that target the ion channel might offer an effective treatment to slow or prevent scarring of the kidney, the primary manifestation of the disease seen in patients, the researchers said. Such channels are pore-like proteins in the membranes of cells thought to control the flow of calcium.

"This gene represents the first ion channel to be associated with FSGS," Winn said. "It's a new mechanism for kidney disease, which may allow us to advance on new treatments as ion channels are known to be amenable to drug therapy."

Winn, along with senior authors Jeffery Vance, M.D. and Paul Rosenberg, M.D., also of Duke, published their findings May 5, 2005, in Science Express, the early online version of the journal Science.

In the United States, the prevalence of FSGS is increasing yearly, with a particularly high incidence among African-Americans, Winn said. The disease attacks tiny filtering units within the kidney called glomeruli -- leading to scarring, or hardening, of this filter. Symptoms of the disease include high blood pressure, an excess of protein in the urine
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Contact: Kendall Morgan
kendall.morgan@duke.edu
919-660-1306
Duke University Medical Center
5-May-2005


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