The largest grant ever awarded by the National Institutes of Health for diabetes research has gone to a University of Utah physician.
Dr. Wayne A. Border, professor and chief of the Division of Nephrology at the U. School of Medicine, will receive $1.2 million over the next five years to expand his research into the causes and possible prevention of kidney disease - particularly that caused by diabetes.The grant announcement Wednesday comes on the heels of a major discovery by a team of Utah and California researchers that may allow physicians to prevent the most common cause of kidney disease.
The disease is glomerulonephritis - an inflammation of the glomeruli, the tiny filtering units in the kidney. Glomerula disease affects more than 200,000 Americans annually. Patients are treated with dialysis or transplantation, at a cost of more than $2.5 billion annually to the federal government.
In July, Border announced that the teams had found that a growth factor, called transforming growth factor beta (TGF-B), could make cultured kidney cells increase production of adherent proteins much the same way the process occurred in diseased kidneys.
When studying TGF-B in rats with kidney disease, Border and associates at the U. found evidence of abnormally high levels of TGF-B in the rodents' inflamed kidneys. They suspected it was responsible for clogging the filtering apparatus by causing an accumulation of adherent proteins.
To prove this new role of TGF-B, the teams prepared antibodies capable of neutralizing the activity of TGF-B. When injected in rats, the antibodies prevented the rats' kidneys from producing excess amounts of adherent proteins. In fact, within seven days of the injection there was no evidence of injury to the rodents' kidneys caused by glo-mer-u-lo-ne-phri-tis.
"An exciting part of this work is not only that we believe we have found that TGF-B stimulates the growth of the extracellular matrix that causes kidney disease, but that we can develop antibodies and drugs that inhibit or actually stop its action, preventing the disease," Border said.
A treatment, now being developed by the teams, also could be effective in combating other kidney disease caused by diabetes, lupus and hypertension and lung diseases, including adult respiratory distress syndrome, he said.
NIH apparently agrees.
The $1.2 million awarded to Border and associates will be used to determine if the transforming growth factor plays a similar role in the development of kidney disease in diabetics.
"This new grant enables us to determine if TGF-B plays the same role in diabetes-caused kidney disease as it does in glomerulonephritis," Border said. "It is an incredible combination of basic and clinical research that may well benefit patients in the relatively near future."
Literally thousands of patients could benefit.
Healthy kidneys function as both a sieve, in which blood is cleansed of water and cellular wastes, and as a filter, through which blood circulates on its way to nourish the body. Waste products are eliminated as urine. When the kidneys fail, death can result.
Kidney failure can be caused by diabetes, high blood pressure and several forms of disease - the most common of which is glomerulonephritis, the subject of the team's initial research.
Border said the new research will be conducted on rats and on human kidney tissue taken during routine kidney biopsies on patients at the U. Medical Center.
The project, however, is a collaborative effort among Border; Dr. Erkki Ruoslahti, cancer researcher and president of the La Jolla Cancer Research Foundation; and Dr. Michael Sporn, chief of the National Cancer Institute's Laboratory of Chemoprevention.