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Scientists learn more about how kidneys fail and how new drugs may intervene

Scientists are learning more about how protein gets in the urine when the kidneys begin to fail and how a new drug blocks it.

"We have known for a long time that renal failure comes with protein in your urine, especially in diabetes," said Dr. David Pollock, renal physiologist at the Medical College of Georgia Vascular Biology Center. It's also known that a new class of drugs called endothelin A receptor antagonists reduce protein in the urine.

New research published in the journal Hypertension connects the two, providing more information about how new drugs under study for kidney failure work.

The scientists have shown in rats that increased levels of the peptide endothelin 1 characteristic of conditions such as diabetes and high-salt diets increase the permeability of tiny kidney filters. The filters recycle key components such as red and white blood cells and proteins, including albumin, that help keep blood vessels from leaking fluid.

The increased permeability causes the proteins to be eliminated in the urine, resulting in a double whammy that likely includes generalized body swelling and further kidney damage. "Without albumin, the fluid just goes into your tissue," Pollock said.

"This filter, which is like cheesecloth, gets damaged in kidney failure and so you get more of these proteins in your urine. Filters start scarring over, you lose the nephron (the filter and its associated kidney cells) and so the kidneys slowly die," he said.

And that's just part of the damage. High endothelin levels also trigger inflammation, sending out proinflammatory molecules that attract inflammatory cells like white blood cells and macrophages to the kidneys, MCG researchers have shown. They also have shown that endothelin A receptor antagonists reduce this inflammatory response.

"There has been no drug that really targets diabetic nephropathy," said Mohamed A. Saleh, MCG graduate student and t

Contact: Toni Baker
Medical College of Georgia

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