Kidney Damage and High Blood Pressure

Research suggests that faulty filtration allows detrimental enzymes to wreak havoc on fluid balance

Newswise — Bethesda, Md. (Sept. 22, 2011) – The kidney performs several vital functions. It filters blood, removes waste products from the body, balances the body’s fluids, and releases hormones that regulate blood pressure. A number of diseases and conditions can damage the kidney’s filtration apparatus, such as diabetes and immune disorders. This damage leads to a condition called nephrotic syndrome, which is characterized by protein in the urine, high cholesterol and triglycerides, and swelling (edema). People with nephrotic syndrome retain salt and water in their bodies and develop swelling and high blood pressure as a result.

Scientists have now begun to understand kidney damage on a cellular level and how the activity of certain molecules in damaged kidneys contributes to salt and water retention in nephrotic syndrome. Several new insights in this area of research will be presented at the7th International Symposium on Aldosterone and the ENaC/Degenerin Family of Ion Channels, being held September 18-22 in Pacific Grove, Calif. The meeting is sponsored by the American Physiological Society.

Faulty FiltrationThe kidneys are marvels of filtration, processing roughly 150 to 200 quarts of blood each day through tiny structures called nephrons. There are about 1 million nephrons per kidney, and each nephron consists of a filtering unit of blood vessels called a glomerulus, which is attached to a tubule. Filtered blood enters the tubule, where various substances are either added to or removed from the filtrate as necessary, and most of the filtered sodium and water is removed. The filtrate that exits the tubule is excreted as urine.

In nephrotic syndrome, a damaged filtration barrier allows substances that are not normally filtered to appear in the filtrate. One of these substances is the protein plasminogen, which is converted in kidney tubules to the protease plasmin. In their research, Thomas R. Kleyman, Professor of Medicine and of Cell biology and Physiology at the University of Pittsburgh School of Medicine and the Symposium’s co-organizer, and Ole Skøtt, Professor of Physiology and Pharmacology and Dean at the University of Southern Denmark in Odense, independently found that plasmin plays a role in activating the epithelial sodium channel (ENaC) on cells in the nephron. ENaC is a protein embedded in cell membranes that facilitates the absorption of filtered sodium from tubules. When ENaC is becomes overactive, excessive absorption of filtered sodium may lead to sodium and water retention.

According to Dr. Kleyman, these findings provide an explanation of how damage to the glomeruli in the kidney’s nephrons leads to edema and high blood pressure. Dr. Kleyman explains: “When plasminogen is cleaved, it can act on several targets. One of those targets is ENaC. Another is the protein prostasin, which, once cleaved, will activate ENaC, as well.”

Dr. Kleyman noted the implications these findings have for treating edema and high blood pressure in patients suffering from nephrotic syndrome. “This is important because if plasmin activates ENaC, it suggests that targeting ENaC in the kidneys with ENaC inhibitors may be a treatment option.”

PresentationsDr. Skøtt will discuss the Danish team’s research in his presentation, “Plasmin, ENaC, and Nephrotic Syndrome,” on Thursday, Sept. 22. Ossama B. Kashlan, Research Assistant Professor of Medicine in the Renal-Electrolyte Division at the University of Pittsburgh, will discuss the molecular mechanisms by which proteases activate ENaC in his presentation, “Conformational Trapping of the Closed State of ENaC” on Monday, Sept. 19.

About the ConferenceThe 7th International Symposium on Aldosterone and the ENaC/Degenerin Family of Ion Channels explores the relationship between fluid regulation and hypertension, the cardiovascular system and other organ systems. The American Physiological Society is sponsoring the conference being held September 18-22, 2011 in Pacific Grove, CA. Additional information can be found online at http://www.the-aps.org/press/releases/11/24.htm.

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NOTE TO EDITORS: For an abstract of any of the above presentations, or to schedule an interview with one of the presenters, please contact Donna Krupa at 301.634.7209, [email protected].

Physiology is the study of how molecules, cells, tissues and organs function to create health or disease. The American Physiological Society has been an integral part of the discovery process since it was established in 1887. To keep up with the science, follow @Phyziochick on Twitter.