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Coronary Artery Calcification Treated with Dialysis
An article published in today's New England Journal of Medicine from researchers at UCLA reports that nearly 90 percent of young adults undergoing dialysis had signs of coronary artery calcification - and that in most patients, the amount of calcification doubled within two years. The dramatically abnormal findings, especially in such a young age group, surprised the study's authors.
The UCLA findings showed that all patients with coronary artery calcification ingested nearly twice as much calcium through phosphate-binding agents, had higher serum phosphorus levels and had more calcium-phosphorus ion products in their bloodstream compared to patients without signs of calcification.
"This is the first study to show the extent of this particular form of cardiovascular abnormality in younger patients on long-term dialysis," said UCLA pediatric nephrologist Isidro B. Salusky, the study's senior author. "Based on radiographic evidence, we are concerned that many young adults with end-stage renal disease have clinically silent, but potentially serious, coronary artery lesions."
Coronary artery calcification represents the deposition of calcium in the wall of vessels that supply blood to the heart. The condition - virtually unheard of in healthy men and women between the ages of 20 and 30 - occurs in only 10 percent of women and 25 percent of men between the ages of 40 and 49 years.
For adults, calcification in the coronary arteries is associated with arteriosclerosis and an increased risk of cardiovascular disease. Cardiovascular disease accounts for nearly 50 percent of all deaths in dialysis patients. The National Kidney Foundation Task Force on Cardiovascular Disease found that the incidence of death from cardiovascular disease among dialysis patients is 10 to 20 times higher than in the general population.
"Based on this study's findings, physicians caring for dialysis patients may want to reconsider the use of large doses of calcium-containing medications in patients who are treated with dialysis," said William Goodman, of UCLA's School of Medicine and the study's lead author.
Study Details
Cardiovascular disease is common in adults receiving regular dialysis, but scientists know little about the prevalence of cardiovascular disease in younger dialysis patients, according to Goodman. He said the study was undertaken to determine the presence and extent of coronary artery calcification in children, adolescents and adults less than 30 years of age undergoing regular dialysis.
Researchers used electron beam computed tomography, a non-invasive method of obtaining a computer image of the target artery, to detect coronary artery calcification in 39 dialysis patients between the ages of 7 and 30 years, and in a control group of 60 men and women with normal renal function between the ages of 20 and 30 years. Repeat electron beam computed tomography scans were taken in a subset of patients after 18-24 months.
The results showed markedly higher coronary artery calcification scores in men and women less than 30 years of age who were treated with regular dialysis than in volunteers of the same age and sex with normal renal function. Fourteen of 16 dialysis patients between the ages of 20 and 30 showed signs of calcification, while no patients under the age of 20 had evidence of calcification. Only five percent of healthy volunteers had calcifications that were detectable by the same method.
In addition to having a two-fold higher daily intake of calcium through phosphate-binding agents compared to patients with no signs of calcification, patients with positive signs of calcification had higher serum phosphorus levels and more calcium-phosphorus ion products in their bloodstream. Calcification scores doubled within 18-24 months in nine out of 10 patients who had detectable calcium deposits at the beginning of the study.
Several established cardiovascular risk factors - such as blood pressure, male gender and diabetes - were not associated with the presence of coronary artery calcification in those undergoing dialysis.
Study Implications
According to Salusky, factors that may be responsible for the development of coronary calcification in dialysis patients include:
-- Greater daily intake of calcium as a phosphate-binding agent
-- High serum phosphorus and high calcium-phosphorus ion products
-- Prolonged treatment with dialysis
-- Older age of study participants
Ninety-five percent of all dialysis patients take phosphate-binding medications to control serum phosphorus levels; 80 percent of these patients are currently on a calcium-based binder.
According to the United States Renal Data System, an estimated 257,000 people in the U.S. now undergo dialysis for kidney failure, also called end-stage renal disease (ESRD). The number of kidney dialysis patients has grown 6.5 percent annually since 1997. Patients on dialysis are at high risk for developing dangerously elevated blood levels of phosphorus and calcium. If left untreated, the combination of high phosphorus and calcium levels in the blood can lead to cardiac and other soft tissue calcifications, renal bone disease and possibly death.
The National Kidney Foundation, which is dedicated to improving the health and well-being of individuals and families affected by kidney diseases, has called for an increase in clinical research concerning cardiovascular disease in patients with kidney disease.
"The mortality rate for dialysis patients due to cardiovascular disease is well documented," said Andrew Levy, a nephrologist at New England Medical Center, Tufts University, Boston, and spokesperson for the National Kidney Foundation. "It is clear that we need to change the way we manage these patients to help avoid the risk."
In addition to Goodman and Salusky, other researchers that contributed to the study include Jonathan Goldin, M.D., Ph.D.; Dr. Beatriz D. Kuzon; Chun Yoon, M.D., Ph.D.; Barbara Gales, R.N.; Donna Sider, R.N.; Yan Wang, Ph.D.; Joanie Chung, M.S.; Aletha Emerick; Lloyd Greaser, M.P.H.; and Robert M. Elashoff, Ph.D.; all with the UCLA School of Medicine.
The study was supported, in part, by United States Public Health Services grants DK-52905, DK-35423, and RR-00865 and by funds from the Casey Lee Ball Foundation.
-UCLA- RYM240
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