Researchers at Yale 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 U.S. have kidney impairment and 500,000 have end-stage kidney 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,” said Jianchao Xu, M.D., associate research scientist, attending physician 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.
While the kidneys remove waste and extra water from the body and control the balance of certain chemicals in the blood like sodium, phosphorus and potassium, by regulating the body water volume, they also have another function. They secrete hormones, like rennin and erythropoietin, into the blood to regulate blood pressure and red cell production.
Xu along with Gary V. Desir, M.D., 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 that “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, Peili Wang, Heino Velazquez, Yanyan Li, Yanling Wu, Aldo Peixoto, and Susan Crowley from Yale and the VACHS and Xiaoqiang Yao from the Chinese University of HongKong. Funding was from the Veterans Administration and grants from the National Institutes of Health.
Citation: Journal of Clinical Investigation (May 2005) early online April 7.
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