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Kidney Cysts: Not All Created Equal

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Friday, January 18, 2008 at 3:33:22 PM
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Researchers at Johns Hopkins have discovered a window in kidney growth that affects the onset of polycystic kidney disease and can mean, in mice, the difference between developing severe cystic disease early in adolescence or late in adulthood.

In the December issue of Nature Medicine, the team reports that genetic mutations acquired before this window result in immediate disease onset whereas those acquired after don’t give rise to disease until late adulthood.

“The question we want to answer is when do these cysts form?” says Gregory Germino, M.D., a professor of nephrology and member of the McKusick-Nathans Institute of Genetic Medicine at Hopkins. “If the cysts form slowly throughout life, that’s one issue, but if they all form while you’re young, then in theory it might be possible to go in there and knock out their growth and the disease will be gone.”

Polycystic kidney disease refers to a group of disorders that cause multiple cysts to grow throughout the kidneys. The most common form is caused by a faulty version of the gene Pkd1. Most people affected develop the condition in late adulthood.

To pinpoint exactly when cysts start forming, the research team knocked out the Pkd1 gene in mice at different times. Knocking out Pkd1 two days after birth caused grossly enlarged kidneys to develop within two weeks.

“Since that didn’t mimic the human condition at all, we then started knocking out Pkd1 in older mice,” says Klaus Piontek, Ph.D., a nephrology research associate at Hopkins.
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