It is important to note that interpretation of the aforementioned studies must be tempered by the fact that intermediate end points were used. To date, only one randomized, prospective study has examined the effect of phosphate binder choice on mortality. The Dialysis Clinical Outcomes Revisited (DCOR) study was a multicenter, open-label trial that randomized 2,103 Medicare patients receiving HD to either sevelamer or calcium salts (calcium carbonate or acetate) (Kidney Int. 2007;72:1130-1137).

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The primary study end point was all-cause mortality during treatment. The DCOR study found no difference in mortality between the sevelamer and calcium groups. The secondary end point of cardiovascular mortality was also not significantly different. Thus, the DCOR study does not support a mortality benefit from treatment with sevelamer over calcium salts.


Cost may play a role in the selection of phosphate binder. The yearly cost for using sevelamer (eight tablets daily) is approximately $4,200 compared with $500 per year when using calcium acetate (even less for calcium carbonate). The yearly costs for the other noncalcium-based binder, lanthanum, would range from $2,400 to $4,800 per year.

A recent report highlighted the economic impact of adherence to the Kidney/Disease Outcomes Quality Initiative guidelines for bone metabolism, noting that expenditures of $781 million annually would be attributed to the use of the recommended agent, sevelamer (Kidney Int. 2004;66:1239-1247). This is a substantial financial burden considering the lack of data substantiating improved outcomes with the use of sevelamer and the potential for bundling by Medicare.

The association of hyperphosphatemia and increased mortality among ESRD patients has been well documented, but only recently has there been any evidence that the use of phosphate binders affects mortality in this population (J Am Soc Nephrol. 2008; published online ahead of print).  In a prospective, observational cohort of 10,044 incident dialysis patients, investigators reported that treatment with phosphate binders is independently associated with improved survival.

This finding is encouraging given the large amount of resources devoted to phosphorus control. But the study results also highlight the need for well-designed prospective, randomized, controlled clinical trials to evaluate hard clinical outcomes, such as cardiovascular and all-cause mortality. The design of new studies will need to account for the myriad other factors that may influence these outcomes. Cost-effectiveness analysis will be necessary to evaluate the financial burden of the various therapies.


Hyperphosphatemia is an independent risk factor for mortality in CKD. The relationships among hyperphosphatemia, phosphate binders, vascular calcification, and mortality are complex.

Our clinical responsibility is to control serum phosphate levels with the range of agents available. Each of these agents has its own advantages and disadvantages. Combination therapy, constant vigilance, and patient-specific education and therapy may help improve outcomes.

Dr. Coladonato is the medical director of South Greensboro Kidney Center, Carolina Kidney Associates, in Greensboro, N.C.