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Keep the baby, toss the bathwater: How kidneys retain proteins, discard waste

St. Louis, July 26, 2006 -- New research may finally settle a decades-old debate about how the kidney keeps valuable blood proteins from harmfully slipping into the urine, a serious health symptom that often precedes kidney failure.

In genetically modified mice, scientists at Washington University School of Medicine in St. Louis captured images of a defective version of a kidney structure leaking a substance from the blood into the urine. The images suggest that the structure, known as the glomerular basement membrane (GBM), normally plays a key role in keeping blood proteins out of the urine.

The finding, reported in the August issue of the Journal of Clinical Investigation, will help doctors understand nephrotic syndrome, a condition with symptoms that include blood proteins in the urine. The syndrome can be triggered by a variety of genetic and environmental factors and leads to kidney failure over a varying time period.

"All the treatments we now use for nephrotic syndrome are either non-specific, meaning that we can't say for sure that they directly address the problem, or they are toxic," notes lead author George Jarad, M.D., a postdoctoral research scholar. "The first step to developing a specific treatment is to understand exactly what's happening. We have to know the details of the process before we can devise a remedy."

The new results are a reversal for nephrologists, who until a decade ago had long suspected the GBM was the primary barrier that retained blood plasma proteins. In the late 1990s, though, a Finnish research team bumped another structure, the slit diaphragm, into the position of prime suspect. They showed that a mutation in one of the proteins that make up the slit diaphragm caused a form of kidney disease that led to protein in the urine.

Both the slit diaphragm and the GBM are found in the glomeruli, small structures within the kidney that filter wastes from the blood and release them i
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Contact: Michael C. Purdy
purdym@wustl.edu
314-286-0122
Washington University School of Medicine
1-Aug-2006


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