Lowly kidney 'gets respect'

with $4 million grant

The kidney is more than just the useful organ that allows us to eat and drink at our favorite pizza joint. To Doug Eaton it is a tightly knit office whose ability to function depends on its workers, or cells, communicating-answering phones, making calls, exchanging messages.

Eaton, an associate professor of physiology and pediatrics who specializes in kidneys, is the lead investigator on a new $4 million federal grant to study how kidney cells communicate not only to rid the body of waste, but more importantly, to maintain blood pressure.

Although the kidney often "gets no respect,'' said Eaton, its impact on our health can be enormous. Kidney disease is the third most common cause of death in the United States and is rapidly gaining on No. 2, stroke.

"The kidney really has bad press, as far as organs go,'' he said. "People do not appreciate what the kidney is there for. It does get rid of waste, but the real reason that the kidneys are there is to make sure your blood pressure is regulated normally. Although your heart, brain and some other organs are responsible for moment-to-moment changes in blood pressure-when you get angry, hop up from your chair, get really excited-the kidney is the body's thermostat. It sets the stable level of blood pressure."

The kidney controls blood pressure by controlling the amount of water in urine to manage the level of blood, and by regulating the body's salt. Any abnormality of kidney function is likely to lead to chronic changes in blood pressure, he said.

Learning how the kidney cells communicate to maintain this complex balance of salt and fluid will help researchers better understand how kidney diseases begin and, some day, how to better treat patients with those diseases, Eaton said.

The grant, from the National Institutes of Health, will fund four related projects over the next five years. The studies look at different aspects of renal function, all focusing on how renal cells communicate to regulate blood pressure.

One aspect will examine how genetic changes in a type of kidney cell affect the amount of salt in the blood. The genetic changes occur in a special protein molecule, called a sodium channel, which is only found in these cells. Typically, the channel proteins act as a gatekeeper, retaining salt in the kidney or allowing it to enter the bloodstream in response to changes in blood pressure. But Eaton has found that small mutations in these channels cause them to retain too much salt. That can lead to high blood pressure, or hypertension. Hypertension affects an estimated 62 million Americans and is a major underlying cause of heart attacks, heart failure and strokes, as well as kidney failure.

A second study may uncover why another group of kidney cells, called mesangial cells, balance the body's salt and liquid to help regulate the body's amount of blood and blood pressure. When the kidney is faced with a lot of salt from food or liquid, the mesangial cells are put on alert. But in some people, particularly diabetics, the cells do not respond. The body's supply of blood becomes abnormally high or low, putting the body's blood pressure out of whack.

How the kidney changes the concentration of urine as it regulates blood pressure will be the focus of the third study. To change the concentration, the kidney can get rid of more fluid without getting rid of salt, or flush out more salt without losing fluid. But, Eaton said, the two usually go hand in hand. So the researchers are trying to learn how the kidney regulates concentrations,'' Eaton said.

Finally, researchers will look at how the kidney's mesangial cells take direction from the endothelial cells, which control how much blood flows through the kidney. One way the body can regulate rising blood pressure is to squeeze more fluid from the blood and send it to the kidney to turn into urine. That process begins with a message from the endothelial cells, telling the mesangial cells to let more fluid pass through. In diabetics, however, the communication link is sometimes broken, Eaton said. The researchers on this study want to know how that link works.

The NIH grant is an interdepartmental and multi-institutional effort involving the Center for Cell and Molecular Signaling and the departments of Medicine, Physiology and Pathology at Emory, the Department of Physiology at Morehouse Medical School and the Department of Medicine at the University of Pennsylvania.

Recently, Eaton was named chairperson of the General Medicine B Study Section, Division of Research Grants for the National Institutes of Health, through June 30, 1998. Members are selected on the basis of their demonstrated competence and achievement in their scientific discipline as evidenced by the quality of research accomplishments, publications in scientific journals and other significant scientific activities, achievements and honors.

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