TUESDAY, March 15 (HealthDay News) -- People with chronic kidney
disease routinely undergo tests to measure blood levels of
phosphorous, calcium and parathyroid hormone, to assess their risk
of heart disease.
However, a new analysis of research stretching back more than 60
years casts doubt on the usefulness of some of those tests.
Researchers found little evidence to support the notion that
these "biomarkers" can diagnose or prevent potential heart trouble,
especially in the case of calcium and parathyroid hormone. The
analysis did confirm an association between high levels of
phosphorus in the blood and mortality in people with kidney
"The studies that show connections between phosphorus, calcium and parathyroid hormone with important health outcomes [death and cardiovascular disease] are too few and suboptimal. Therefore, they cannot provide good evidence for definite target levels, particularly for calcium and parathyroid hormone," said study senior author Dr. Giovanni FM Strippoli, scientific director of Diaverum and renal research coordinator at the Mario Negri Sud Consortium in S. Maria Imbaro, Italy.
"People with kidney disease have mortality rates much higher than the general population. The key problem, however, is that mortality in these patients has not decreased, despite several years of new treatments becoming available," he noted.
One problem is that "risk factors for disease have become
confused with the disease itself," Strippoli said. "Now, it appears
that many of the risk factors we have identified so far either are
not really risk factors, or we have no drugs to appropriately treat
them to improve health outcomes."
The findings are published in the March 16 issue of the
Journal of the American Medical Association.
About 26 million Americans have chronic kidney disease,
according to the National Kidney Foundation, and heart disease
remains a major cause of death in people with chronic kidney
Current clinical practice guidelines recommend testing for
phosphorus, calcium and parathyroid levels in the blood, and
treating abnormal levels of these biomarkers.
For the current study, the researchers reviewed all available
literature from 1947 through 2010. They found 47 studies of these
biomarkers to include in their analysis.
The team found that the risk of death increased 18 percent for
each 1 milligram per deciliter increase in serum [blood]
phosphorous. However, they found no association between mortality
and parathyroid hormone levels or calcium levels.
Strippoli added that there were no good studies conducted to
assess whether or not the treatment of high phosphorus levels could
have an impact on the risk of death.
"The idea that we can measure things in the blood in people with chronic kidney disease and make very informed, individualized treatment decisions for patients should be dispelled," said Dr. Bryan Kestenbaum, author of an accompanying editorial in the same issue of the journal.
There are plausible biological reasons for suspecting that
phosphorous and calcium could increase the risk of heart disease,
as they may affect the flexibility of vessel walls. Parathyroid
hormone can have direct effects on heart cells and may make them
grow abnormally, he explained, but added that no one can show a
direct cause-and-effect relationship for any of these
"Even though this analysis found an association between increased phosphorus levels and mortality, we just don't know if there's cause and effect. Is it the phosphate that causes the increased risk, or is it something about people with high phosphate levels that makes them have a higher risk?" said Kestenbaum, an associate professor in medicine and epidemiology at the Kidney Research Institute at the University of Washington in Seattle.
He added that the challenge for physicians is to try to figure
out what to do now. The treatment to lower phosphate levels is
simple and has a very low side effect profile. And, because there's
some evidence that people with high phosphorus levels have an
increased cardiovascular risk, most physicians would "err on the
side of treating." But, he said, there's really "no proof that
treatment would lower the risk. We really need a randomized,
controlled trial to assess the risk," he said.
Strippoli agreed that a randomized clinical trial of a
phosphate-lowering drug is the only way to know for sure if there's
a cause-and-effect relationship.
He also believes that there needs to be a shift in medicine away
from treating blood biomarkers.
"Times have changed. In the past, our patients were really very compromised. Nowadays, they are better treated overall, perhaps meaning that less emphasis on the micromanagement of individual biomarkers is required. We need to treat diseases, not biomarkers."
Learn more about chronic kidney disease from the
National Kidney Foundation.
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