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Breakdown of kidney's ability to clean its own filters likely causes disease
Date:1/29/2008

plasma proteins are albumin, which helps regulate blood volume and convey a number of different substances around the body, and immunoglobin G (IgG), a type of immune system antibody. Because they're so common, we figured they would be among the most likely to get stuck on the filter, and set out to look for proteins that help clear them."

Researchers looked for proteins made in podocytes that could bind to albumin and IgG, reasoning that such proteins likely provide the "handles" the podocytes need to grab proteins and clear them from the filter.

A protein known as FcRn was high on the list of likely suspects. Akilesh had studied FcRn previously in the laboratory of coauthor Derry C. Roopenian, Ph.D., professor at the Jackson Laboratory in Bar Harbor, Maine. Prior research there and in other laboratories had revealed that FcRn binds to both IgG and albumin and is present in human podocytes.

After confirming that the FcRn protein also is made in mouse podocytes, scientists then asked if FcRn was responsible for clearing IgG antibody from the filter. To do this, they measured the retention of a radioactive tracer in the kidneys of normal mice and in mice where the gene for FcRn had been disabled. Mice lacking FcRn had difficulty clearing antibody from the kidney.

When researchers studied the mice lacking FcRn for longer periods of time, they saw evidence that antibodies were accumulating in the kidney.

In another experiment, researchers gave the mice injections of large quantities of protein to saturate the clearance system. They followed those injections with what would normally have been a harmlessly small dose of an antibody potentially toxic to the kidney. The mice developed kidney damage as a result. Researchers believe this was because they couldn't clear the toxic antibody from the GBM quickly enough.

"This is the first clear demonstration that the filter system in the kidney isn't just a passive mech
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Contact: Michael C. Purdy
purdym@wustl.edu
314-286-0122
Washington University School of Medicine
Source:Eurekalert

Page: 1 2 3

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