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Pharmacology, efficacy and safety of oral phosphate binders

Abstract

The ideal serum level of phosphate in patients on dialysis, and the benefits of controlling levels of phosphate in serum remain unclear despite observational studies that associate phosphate levels with mortality. In the absence of robust data from trials, current guidelines are necessarily based on opinion. Oral phosphate binders are required by the majority of patients on dialysis, and all of these binders can control serum levels of phosphate to similar degrees. Patient preference and adherence to prescribed therapy is at least as important as the efficacy of the prescribed binder. Avoidance of calcium-containing binders has become accepted practice where the alternatives are affordable, but incontrovertible evidence in favor of this approach is lacking. Use of sevelamer and lanthanum avoids calcium loading, but at considerable financial cost and with no reliable patient outcome data to prove their value. Additional approaches to aid control of serum levels of phosphate include blockade of gastrointestinal phosphate absorption and possibly binding of salivary phosphate. Importantly, the role of phosphate control in determining patient outcomes must be quantified, which is likely to require a large randomized, controlled study of two levels of phosphate control. Without such a study we will continue to rely on observational data with all its uncertainties and potential to mislead.

Key Points

  • The ideal serum level of phosphate and the benefits of controlling phosphate levels in serum remain unclear, and available guidelines are largely based on opinion

  • All phosphate binders can control phosphate levels in serum to a similar degree; however, patient preference and adherence to prescribed therapy must be considered together with the efficacy of the prescribed binder

  • Most clinicians avoid calcium-containing binders where the alternatives are affordable, but evidence to support this strategy is limited

  • Calcium loading can be avoided with sevelamer and lanthanum, but these drugs are expensive and no reliable patient outcome data exist to prove their value

  • Alternative approaches to control of phosphate absorption include blockade of gastrointestinal phosphate and possibly binding of salivary phosphate

  • Randomized, controlled trials are required to determine the ideal range for control of phosphate in serum

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Figure 1: Phosphate balance in a patient receiving dialysis.

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Acknowledgements

C. P. Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape, LLC-accredited continuing medical education activity associated with this article.

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All authors contributed equally to researching data for the article, discussion of the content and reviewing and editing the manuscript before submission. A. J. Hutchison wrote the article.

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A. J. Hutchison has received research grants from and previously been a consultant for Amgen. He is a consultant for Fresenius Healthcare. A. J. Hutchison has received research grants from, is a speaker for, and was previously a consultant to, Shire Pharmaceuticals. The other authors declare no competing interests.

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Hutchison, A., Smith, C. & Brenchley, P. Pharmacology, efficacy and safety of oral phosphate binders. Nat Rev Nephrol 7, 578–589 (2011). https://doi.org/10.1038/nrneph.2011.112

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