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These potential benefits of newer agents, including sevelamer, and other anion-exchange resins, as discussed by Drs Wrong and Harland [5], are supported, only in part, by very large-scale observational studies, where lower levels of serum calcium, phosphorus, and less so parathyroid hormone, are associated with improved survival for people with chronic kidney disease [1,6]. As we have previously discussed extensively, this is not enough [7–9]. What remains important is that the direct relationship between modification of calcium, phosphorus or PTH with improved survival and cardiovascular outcomes in randomized, controlled trials is still far from proven. This is despite the largest trial in this area, the Dialysis Clinical Outcomes Revisited (DCOR) trial enrolling over 2100 patients to either sevelamer or calcium salts, which showed no difference for mortality between treatment arms [10] and the meta-analyses of phosphate binders [11], calcimimetics [9] and vitamin D compounds [8]. The ongoing search for efficacious and cost-effective agents, such as anion exchange resins, is laudable. Therefore, the suggestion of Wrong and Harland that colestipol, or other cheaper alternatives, could be promoted in preference to the more expensive sevelamer, is appealing. However, while these and other measures may be temporarily supported, the real priority for resources in this area should be directed at understanding the effects of the treatment for altered mineral metabolism on patient centred outcomes, including bone pain, cardiovascular events and mortality in chronic kidney disease. Do any of these drugs, which can control phosphorus levels, really have any effect on reducing the excess mortality which is attributable to high serum phosphorus levels in chronic kidney disease? Certainly there are numerous resins that can be used to absorb intestinal phosphorus, but just as well there are now numerous data to support that adequately powered, randomized trials investigating either pharmaceutical agents or the serum targets of calcium, phosphorus and parathyroid hormone levels should be developed.

Time-dependent effect of sevelamerHCl on the cardiovascular system