When 62-year-old Fred W died
of a heart attack in the middle of his pottery class,
his relatives were surprised — so was his doctor.
Although Fred suffered from chronic kidney disease (CKD),
few people with this illness ever die of kidney failure.
Strangely, an unusually high number of these patients
succumb to cardiovascular diseases — and no one fully
understands why. A study in February's Journal of the
American Society of Nephrology takes a stab at unravelling
this mystery.
It's been observed that among patients
with end-stage renal disease, those with high serum
phosphate levels are most likely to suffer a heart attack.
Many are put on a diet to restrict phosphate intake,
and appear to benefit from it. Whether serum phosphate
is also linked to heart problems in the far larger numbers
of people with milder or asymptomatic kidney disease
is the question researchers at the University of Washington
tried to answer.
CLEAR
AND PRESENT DANGER
The researchers, led by Dr Dennis Andress, analyzed
phosphate levels in 3,490 CKD patients with an average
age of 72 from the Veterans' Affairs hospitals in the
US Northwest, and compared them to rates of all-cause
mortality and heart attack.
The relationship between high phosphate
levels and death from cardiovascular disease was clear
and unequivocal. Within three years of their serum phosphate
being measured, 72% of subjects in the lowest phosphate
quintile were still alive, compared to 67% of the three
middle quintiles and just 56% of those with the highest
levels.
A statistically significant increase
in risk of death was measurable at 3.5mg/dL of serum
phosphate, a concentration which most would consider
to be at the upper end of the 'normal' range. Beyond
that, risk of death increased by 23% for each additional
milligram, and risk of heart attack rose by 35% for
each milligram.
The study subjects were generally
in poor health with many comorbid conditions. Yet when
the phosphate effect was adjusted by controlling for
other risk factors, it remained distinct and robust.
"It is still possible that renal function is confounding
our analyses," concede the authors, who also call for
further research in a less overwhelmingly white male
population than their Veterans' Affairs sample.
This does not prove, the authors
acknowledge, that phosphate is causing heart disease
in renal patients, or that reducing phosphate in their
diet would be protective. It may even be that high phosphate
levels are simply indicative of a less healthy diet,
while some other ingredient in that diet is doing the
actual damage — though there was no correlation
between phosphate levels and lipid profile or body mass
index. The obvious course of action, it seems, would
be to have a go at controlling phosphate levels in pre-dialysis
kidney patients, and see if it helps.
J Am Soc Nephrol Feb 2005;16:520-8
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