Yale Bulletin and Calendar

April 15, 2005|Volume 32, Number 26

Dr. Gary Desir (left) and Dr. Jianchao Xu say that their research on a kidney protein may lead to new treatments for victims of heart attacks.

Researchers identify a protein in the kidney that regulates heart function and blood pressure

Researchers at the School of Medicine and the VA Connecticut Healthcare System in West Haven identified a novel human kidney protein called renalase that regulates both heart contraction and blood pressure, and that is a strong candidate for easily administered treatment of advanced kidney and cardiovascular disease.

Over eight million people in the United States have kidney impairment, and 500,000 have end-stage renal disease (ESRD), for which treatment is often limited to dialysis. Elevated blood pressure and cardiovascular disease are commonly associated problems.

Renalase is secreted by the kidneys and circulates freely in the bloodstream. Patients with kidney disease have very low levels of renalase, suggesting that its absence may lead to the cardiovascular complications found in ESRD.

"This is one of the most exciting findings of kidney metabolism in recent years," says Dr. Jianchao Xu, associate research scientist in the Department of Internal Medicine (Nephrology), attending physician at Yale-New Haven Hospital and lead author. "It has immediate implications for therapy."

Like erythropoietin, the human renalase protein could be injected to replace what is lost in kidney disease, explains Xu.

While the kidneys remove waste and extra water from the body and control the balance of certain chemicals in the blood -- such as sodium, phosphorus and potassium -- by regulating the body water volume, they also have another function. They secrete hormones, like renin and erythropoietin, into the blood to regulate blood pressure and red cell production.

Xu along with Dr. Gary V. Desir, professor in the Department of Medicine (Nephrology) and senior author, screened genetic databases for other hormones produced by the kidney that regulate the cardiovascular system. They discovered renalase, a monoamine oxidase that breaks down catecholamines, such as adrenaline and dopamine.

Desir notes, "We are hopeful that renalase will impact the treatment of chronic kidney disease as favorably as erythropoietin, and change the way in which we treat patients with chest pain and heart attacks."

Other authors include Guoyong Li, Dr. Peili Wang, Heino Velazquez, Dr. Yan Yan Li, Dr. Yanling Wu, Dr. Aldo Peixoto and Dr. Susan Crowley from Yale and the VA center, and Xiaoqiang Yao from the Chinese University of Hong Kong. Funding was provided by the Veterans Administration and grants from the National Institutes of Health.

-- By Janet Rettig Emanuel

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