Doctors find a new heart drug in kidney

Yale researchers have identified a new kidney protein that soon may become a viable treatment for patients with cardiovascular problems related to advanced kidney disease.

The protein, called renalase, is produced and transferred to the blood by the kidney and regulates heart contraction, heart rate and blood pressure, said Dr. Jianchao Xu, an associate research scientist at the Yale School of Medicine and one of the project’s principal investigators. The study was published online in the Journal of Clinical Investigation in April 2005.

According to the American Society of Nephrology, about 20 million Americans have kidney disease, while approximately 500,000 suffer from End-State Renal Disease, a complete or near-complete failure of the kidney.

Individuals who suffer from kidney disease or failure have a greater risk of developing cardiovascular disease because the kidney and heart work together to regulate blood flow to the organs and tissues of the body, said Dr. Forrester Lee, a professor at the medical school and a cardiologist at Yale-New Haven Hospital.

“In states of heart failure or kidney failure, the neurohormonal regulatory mechanisms [through which the heart and kidney interact] break down. This failure of regulation can lead to disease of the heart or the kidney,” he said.

In 1999, Xu initiated a project to identify and isolate all the proteins made by the kidney in an effort to explain why patients with severe kidney disease, even those undergoing dialysis, have a predisposition toward cardiovascular problems and high mortality rate.

“The kidney has an important function which the artificial kidney cannot replicate,” he said. “[It] makes useful proteins that regulate body functions.”

While the early years of the study were largely unfruitful, the advent of technology associated with the Human Genome Project allowed the researchers to identify over 100 proteins secreted by the kidney, one of which was renalase, Xu said.

Renalase reduces the amount of adrenaline present in the bloodstream, thereby regulating heart contraction and blood pressure, said Dr. Gary Desir, a nephrology professor at the medical school and senior investigator in the study.

The scientists said they hope replacing renalase in the blood of patients who have lost kidney function will reduce the number of associated cardiovascular complications.

Desir said he does not anticipate problems with this treatment because renalase is naturally found in the bloodstream.

“Since it’s a normal component of blood, there really shouldn’t be much trouble making it suitable for human use,” he said. “If we start development now, we should be able to make it available for humans within a year or so.”

In addition, the protein could possibly treat people with too much adrenaline in their blood, which can lead to heart failure, chest pain and heart attack, but Desir said additional research will be necessary.

Desir said his lab has learned how to synthetically make renalase and has successfully completed animal trials.

“We’ve already tested in animals,” he said. “Basically what we have to do now is set up some therapeutic human studies.”

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