016-AP-02



Finding Could Lead to Treatments for Complication Found in Nearly All Kidney Disease Victims

Irvine, Calif., Jan. 22, 2002 -- A UC Irvine College of Medicine study has identified key cellular interactions that lead to cardiovascular problems that plague nearly all people with kidney failure.

The study, conducted on rats, indicates that low levels of an enzyme and cellular receptor help produce the high lipid levels that help increase rates of cardiovascular disease in kidney patients. The research may lead to effective treatment for the heart and blood vessel disease that accompanies kidney failure. The study appears in the January issue of Kidney International.

Dr. Nick Vaziri, professor of medicine and chief of nephrology at UCI Medical Center, and his team found that naturally occurring kidney disease in rats led to very low levels of an enzyme and cellular receptor that play a major role in the processing of fat molecules from the blood. The resulting high levels of fat molecules, known as very low-density lipoproteins or "bad cholesterol," are major risk factors for cardiovascular disease.

More than 300,000 people are treated for kidney failure in the United States every year, a number that has doubled in the past 15 years, according to the U.S. Public Health Service. Half of all kidney failures are caused by diabetes; the rest is caused by high blood pressure, inflammation, inherited disorders and infections. There is no cure.

"Nearly all kidney failure patients also develop cardiovascular disease, which progresses much more rapidly than it does in people who don't suffer from kidney failure," Vaziri said. "This complication causes many kidney failure patients to die at young ages and is caused partly by high levels of very low-density lipoproteins in the blood. This study helps demonstrate why those high levels arise in kidney failure and may offer a way to handle this deadly complication of the disease."

Vaziri and his team found that the levels of an enzyme, lipoprotein lipase, and of a cellular receptor called VLDL-R were much lower in rats that had kidney disease, compared to normal rats. After 34 weeks in animals with kidney disease, enzyme levels were about two-thirds below that of normal rats, and levels of the receptor dropped by about three-quarters below that of normal rats. In muscle cells, which are greatly dependent upon the very low-density lipoprotein and other fats for energy, levels of the VLDL-R receptor had dropped about 85 percent below normal.

"Normally, muscle and fat cells are able to process fats for immediate energy needs or store the fat for later use," Vaziri said. "We now see that in kidney failure, levels of the receptor and enzyme responsible for taking these fats out of the blood and processing them for the body's energy needs are too low. These low levels lead to dangerous buildup of so-called 'bad cholesterol' in the blood, leading to atherosclerosis and increasing the risk of heart disease so common in kidney failure patients."

Vaziri believes that the low levels of receptors and enzymes limit the body's ability to use the fats for energy production needed by muscles. This limitation may contribute to weakness and low capacity for exercise, commonly seen in patients with advanced kidney failure.

The study suggests that, if the same results are found in humans, increasing levels of the lipoprotein lipase enzyme and VLDL-R could help lower the risk of cardiovascular disease in kidney failure.

Vaziri and his team have spent years detailing the mechanisms in the body that lead to kidney disease and the cardiovascular and neurological complications that arise from the disease. The researchers now are looking at how high levels of fats may contribute to kidney failure itself, in addition to further examining the role of the receptor and lipoprotein lipase in the progression of heart disease.

Vaziri's colleagues in the study included Tadashi Sato and Kaihui Liang, of Saga Medical School, Saga, Japan, and UCI.

###
Contact:
Andrew Porterfield
(949) 824-3969
amporter@uci.edu

UNIVERSITY OF CALIFORNIA, IRVINE: A TOP-10 PUBLIC UNIVERSITY

A complete archive of press releases is available on the World Wide Web at www.today.uci.edu.