WEDNESDAY, Sept. 22, 2004 (HealthDayNews) -- Kidney disease so mild that a person might not notice it can still increase the risk of heart disease, stroke, and even death, two studies find.
The link between kidney failure and cardiovascular disease has long been known. The two large-scale studies, published in the Sept. 23 issue of the New England Journal of Medicine, show a direct relationship between kidney function that is below normal but not severe enough to cause kidney failure and the risk of major cardiovascular problems and death.
Kidney function is described by the glomerular filtration rate (GFR), which measures the kidney's ability to remove impurities from the blood. Most people have a GFR of 100 or more, said Dr. Alan S. Go, a research scientist at Kaiser Permanente of Northern California, who led one of the studies.
That study included more than 1.1 million Kaiser Permanente adult members, calculating the rate of cardiovascular problems, hospitalizations and death associated with lower-than-normal GFR levels in a follow-up period of nearly three years.
"There appears to be a cutoff at a filtering rate below 60," Go said. "The risk really takes off below 45."
The incidence of cardiovascular problems increased steadily as GFR readings decreased, the study found. Compared to those with a reading of 60 or more, the cardiovascular risk was 40 percent higher for persons with a GFR between 45 and 59. It doubled for readings between 30 to 44 and was 3.4 times higher for readings between 15 and 29.
The death rate followed the same pattern. It was 20 percent higher for GFRs from 45 to 59, 80 percent higher for readings from 30 to 44 and more than three times higher for persons with GFRs between 15 to 29.
The second report looked at a completely different population, more than 14,000 patients who survived heart attacks. It found the same relationship, starting at higher GFR levels. The risk of death or cardiovascular events such as heart attack and stroke went up 10 percent for every 10-point drop in GFR, the study found.
The link between kidney disease and cardiovascular disease have long been established, Go said. The two most common causes of kidney disease are diabetes and high blood pressure, which are also known to be major risk factors for cardiovascular disease.
Kidney disease has its own adverse effects on the arteries, Go explained. "It leads to higher levels of inflammation," he said. "With reduced kidney function, there is a higher likelihood of blood clots. Also, blood vessels get stiffer and less flexible."
Other mechanisms are at work, said Dr. Nick D. Vaziri, a professor of medicine and physiology at the University of California at Irvine, who has done animal studies on the effects of reduced kidney function.
Vaziri has studied the effects of proteinuria, the leakage of protein into the urine that occurs when the kidney does not function normally. He found the same inflammation noted by Go, but also alterations in the way the body manages cholesterol.
"In proteinuria, the level of bad cholesterol rises and the metabolism of good cholesterol is altered," he said.
"Bad" cholesterol is the LDL form, which can accumulate in artery walls. "Good" cholesterol is the HDL form, which escorts fats away from artery walls. When kidney function declines, the altered metabolism of HDL cholesterol means that "cholesterol keeps going into cardiovascular cells but cannot get out, so the cholesterol content of the cell rises," Vaziri explained.
The lesson for people in general and doctors in particular is that "persons with risk factors such as high blood pressure or a family history of cardiovascular disease need to be screened for reduced kidney function," Go said. "If they do have reduced function, there should be more aggressive efforts to control known risk factors for cardiovascular disease, such as blood pressure, cholesterol and diabetes."
Kidney function can be measured by a readily available test for blood levels of creatinine, a muscle-derived protein that is filtered out by the kidneys, he said.
More information
An overview of the relationship between kidney trouble and heart disease can be found at the American Heart Association.
