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Phosphate Binders Spur Cardiac Deaths in Dialysis.

ATLANTA -- Calcium-based phosphate binders, which are widely used to manage hyperphosphatemia in dialysis patients, appear to be an important contributor to the extraordinarily high rate of cardiovascular mortality that is seen in this population.

These calcium-based binders lower serum phosphate levels, but at the same time a huge burden of calcium is accumulated in the patient's body, Dr. Geoffrey A. Block said at a meeting on clinical nephrology that was sponsored by the National Kidney Foundation.

The resultant high calcium-phosphorus product has been clearly shown in the dialysis population to be associated with an increased relative risk of cardiovascular death through the mechanism of vascular and cardiac calcification, Dr. Block said.

Hyperphosphatemia in patients with advanced renal failure promotes secondary hyperparathyroidism as well as renal osteodystrophy. It also promotes vascular and cardiac-valve calcification, he noted.

Ironically enough, the calcium-based binders that are used to control hyperphosphatemia--an important contributor to cardiovascular risk in the dialysis population--exacerbate these same cardiovascular issues even while curbing patients' serum phosphate, explained Dr. Block, a Denver nephrologist.

Cardiovascular disease is the leading cause of death in patients with end-stage renal disease. The cardiovascular mortality rate in these patients is 10- to 20-fold greater than the rate in the age-, race-, and gender-matched general population, he said.

Elevated serum phosphate is a ubiquitous problem in end-stage renal disease because dialysis is inefficient at removing phosphorus from the extracellular fluid. As a consequence, 95% of dialysis patients use phosphate binders in an effort to achieve control of serum phosphorus, Dr. Block said at a session sponsored by Genzyme Corp.

Aluminum-based binders, which were popular in the 1980s, caused toxicity due to total body aluminum accumulation. They were largely replaced by calcium-based binders in the 1990s. Add the calcium obtained from the widely used phosphate-binding agents to the load of absorbed dietary calcium plus the calcium in thrice-weekly dialysate, and the result is "an incredible calcium burden," he stressed.

This extra calcium isn't deposited into bone, either. Indeed, there is a net efflux of calcium from bone in dialysis patients. The calcium is instead deposited in arterial walls, cardiac valves, and viscera, Dr. Block explained.

Preliminary results from Dr. Block's electron beam CT study of 95 dialysis patients showed that nearly half of them had coronary artery calcium scores in excess of 500, which is pretty well off the charts in terms of severity of coronary atherosclerosis. By comparison, a normal score is less than 30.

In other presentations at the conference, several speakers cited Dr. Block's study of more than 6,000 U.S. renal dialysis patients as evidence for more vigorous control of hyperphosphatemia and the calcium-phosphate product in order to improve patient survival.

In Dr. Block's dialysis population, serum phosphorus averaged 6.2 mg/dL; 39% of the patients had levels in excess of 6.5 mg/dL, 30% had levels above 7 mg/dL, and 10% had levels greater than 9 mg/dL. The adjusted relative risk of death for patients whose serum phosphorus was greater than 6.5 mg/dL was 27% greater than for those with a level of 2.4-6.5 mg/dL.

Similarly, patients in the highest quintile for calcium-phosphate product--that is, greater than 72 [mg.sup.2]/[dL.sup.2]--had an adjusted 34% increased relative risk of mortality, compared with those with a product in the 42-53 [mg.sup.2]/[dL.sup.2] range.

Most of these deaths were cardiovascular. For every 10-[mg.sup.2]/[dL.sup.2] increase in the calcium-phosphate product, the relative risk of death climbed by 11%. And for each 1-mg/dL elevation in serum phosphorus, the relative risk of mortality rose by 6%.

"It has become very important to control serum phosphorus to a much greater degree than we have previously been able to achieve," Dr. Block said.

"I would recommend that we aim for a serum phosphorus level between 3 mg/dL and 5 mg/dL as acceptable. We can no longer accept phosphorus levels that are above normal. Similarly, we need to shoot for a calcium-phosphate product below 55 [mg.sup.2]/[dL.sup.2]," he added.
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Publication:Family Practice News
Geographic Code:1USA
Date:Jul 1, 2000
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