Lowering Blood Protein Won't Help Kidney Patients

TUESDAY Sept. 11, 2007 -- Lowering blood levels of an inflammation-linked protein called homocysteine won't help people with serious kidney disease live any longer, new research concludes.

The study, which is published in the Sept. 12 issue of the Journal of the American Medical Association, found that although people who took extra folic acid, vitamin B6 and vitamin B12 were able to significantly lower their homocysteine levels, that change had no effect on their risk of death or heart attack or stroke.

Lowered homocysteine also had no effect on the risk of leg amputations for people with advanced kidney disease or end-stage renal disease.

"We had every expectation at the start of the study that lowering homocysteine would be beneficial," said Dr. Rex L. Jamison, chair and principal investigator for the Homocysteine Study of the Veterans Administration Cooperative Studies Program. "But, our results showed that there was no difference in the number of people who died in the treatment group versus the placebo group, and there was no difference in heart attack, stroke or amputations due to vascular disease," said Jamison, who is professor of medicine at Stanford University School of Medicine.

Numerous studies have linked homocysteine to a variety of bad outcomes, such as heart attack and stroke, leading researchers to believe it might play a role in the development of vascular disease. However, none of the studies has been able to establish a cause-and-effect relationship between homocysteine and disease, leaving open the possibility that high levels of this amino acid might just be a marker of vascular disease, rather than a cause of it.

People with chronic kidney disease or end-stage renal (kidney) disease have much higher levels of homocysteine than the general population, according to the study. And, people with kidney disease also have significantly higher levels of vascular disease than the general population. Complications from vascular disease are so common in kidney patients that as many as one out of every five dies each year from vascular disease, according to the researchers.

Because of the association between homocysteine and vascular disease, Jamison's group hoped that if they could lower homocysteine levels, they could also reduce mortality and the rates of heart attack, stroke and amputations.

They enrolled more than 2,000 veterans at 36 Veterans Administration medical centers across the country. All had advanced chronic kidney disease or end-stage renal failure.

Half of the participants were given a placebo, and the other half were instructed to take a daily capsule that contained 40 milligrams (mg) folic acid, 100 mg vitamin B6 and 2 mg of vitamin B12.

The study lasted five years, and the average follow-up time was 3.2 years.

The vitamin therapy was successful in lowering homocysteine levels. Homocysteine went down almost 26 percent in the treatment group, but less than 2 percent in the placebo group.

However, those lowered levels did not translate into saved lives. In total, 448 people from the vitamin group and 436 people in the placebo group died during the study -- statistically nearly equal. Additionally, the researchers found no statistically significant differences in the rates of heart attack, stroke and amputation.

While this study wasn't designed to determine why lowering homocysteine levels was ineffective in preventing deaths and disease, Jamison said there are several possibilities. "One is that homocysteine is a marker of vascular disease, rather than a cause of it. Another is that the vascular burden in these patients may be too great. It may be that we started too late to make a difference in these patients."

Dr. Robert Provenzano, chief of nephrology at St. John Hospital and Medical Center in Detroit, said he believes this study "puts to rest the idea that homocysteine causes vascular damage. It looks like it's nothing more than a marker for inflammation."

"In my field, this is very important. We've been trying to bring homocysteine down in our patients, hoping it would have a positive impact," said Provenzano. "But, the decrease in homocysteine was quite profound in this study. If there were any benefit, we would have seen it."

If you have kidney disease and are concerned about your kidney health, both Jamison and Provenzano recommended quitting smoking, lowering your cholesterol and blood pressure, staying at a healthy weight and maintaining good blood sugar control if you have diabetes.

More information

To learn more about preventing kidney disease, visit the National Kidney Disease Education Program.

Posted: September 2007


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