Review Article
An Update on Phosphate Binders: A Dietitian's Perspective

https://doi.org/10.1053/j.jrn.2016.01.009Get rights and content

Control of serum phosphorus (PO4) has been long recognized as a goal in the nutritional and medical management of the patients with chronic kidney disease. Phosphate-binding compounds were introduced in the 1970s for the treatment of hyperphosphatemia in patients on dialysis after it was observed that oral administration of aluminum hydroxide as an antacid also reduced serum PO4 levels. Forty years later, aluminum is very seldom used as a phosphate binder as many other safer compounds are now available. This article is a comprehensive review, geared to the renal dietitian, of the most common binder categories. It will discuss pharmacokinetics, side effects, initial and optimal doses, phosphate affinity, and controversies of use. It will also review two novel approaches to serum PO4 management in chronic kidney disease patients receiving dialysis and provide a new calculation by which binders can be compared.

Section snippets

Relative Phosphate-Binding Coefficient and the Phosphate Binder Equivalent Dose

Given the number of phosphate-binding agents, comparison between agents is challenging. Researchers in the Frequent Hemodialysis Network Trial faced this challenge when trying to interpret changes in serum PO4 levels. Their question was how much of the change was due to the increase in dialysis frequency and how much was due to the use of various phosphate binders? Daugirdas et al.24 reviewed stool and urinary in vivo phosphate-binding capacities (PBC) in subjects with non-CKD and CKD.

From

Calcium-Based Binders

Calcium-based–binding agents are the most commonly used medication for serum PO4 control despite multiple studies linking them to coronary and metastatic calcification.6, 8, 9, 10 KDIGO and KDOQI guidelines recommend limiting or avoiding the use of calcium binders in patients who have elevated serum calcium levels, have low serum parathyroid levels, or have known calcification.22, 26 Some studies have shown that many patients have calcification before dialysis is initiated calling into question

Noncalcium/Nonmetal Binders

Sevelamer hydrochloride (Renagel®, Sanofi US, Bridgewater, NJ), and sevelamer carbonate (Renvela®, Sanofi US, Bridgewater, NJ) are the two products currently available in this class. Sevelamer is a nonabsorbable cross-linked polymer that exchanges HCl or carbonate (HCO3−) for PO4 in the GI tract.15, 23 The HCl and HCO3− are absorbed into the body while the resulting PO4-laden polymer passes through the GI tract and is excreted.

In two pivotal studies examining the effectiveness of SH, serum PO4

Lanthanum

Lanthanum carbonate (Fosrenol®, Shire US Inc., Wayne, PA) is the first phosphate-binding compound to use the metal lanthanum to bind phosphate. Each chewable tablet contains lanthanum carbonate hydrate equal to 500, 750, or 1,000 mg of elemental lanthanum. In the GI track, lanthanum binds PO4 to form the nonabsorbable compound lanthanum phosphate. In vitro studies demonstrate that lanthanum binds phosphate at pH levels from 3 to 7. Most phosphate binding to lanthanum occurs at pH levels between

Iron-Based Binders

Sucroferric oxyhydroxide (Velphoro®, Fresenius Medical Care North America) is the first iron-based phosphate binder introduced to North America. Each chewable tablet contains 500 mg of iron equivalent to 2,500 mg sucroferric oxyhydroxide. In the GI tract, phosphate binds to sucroferric oxyhydroxide to form an insoluble compound. The sucrose and starch components of the tablet are absorbed. In vitro studies show that the phosphate binding takes place between pH ranges of 1.2 to 7.5 with a PBC of

Novel Approaches to Phosphate Control

Two novel ways to approach controlling serum PO4 levels used in the past few years are the use of niacin and the use of chitosan-containing chewing gum.

Niacin and nicotinamide reduce phosphate absorption by inhibiting intestinal sodium–phosphate cotransporter-2b. In an 8-week trial using nicotinamide in addition to the patient's PO4 binder, serum PO4 was lowered from 6.45 mg/dL to 5.28 mg/dL.20 Using these products in addition to PO4 binder therapy may be a benefit as it has been shown that

Conclusion

Improving serum PO4 levels continues to be a primary goal in the nutrition and medical management of the CKD patient on dialysis. Multiple strategies are used to control serum PO4 levels including phosphate-binding agents, dietary phosphate restrictions, and adequate dialysis therapy. The number of phosphate-binding agents has increased over the past 40 years giving practitioners a variety of agents and forms (powder, liquid, wafer, pills) to tailor binder regimens to the patient's preference,

Practical Application

Over the last 2 decades, the number of FDA-approved phosphate-binding agents has increased. This article serves as a tool for practitioners to use when comparing potential phosphate binders. Additionally, the phosphate-binding equivalent dose (PBED) in conjunction with package insert dosing instructions can be used to guide dosing when therapies are changed.

Acknowledgments

The author thanks Dr. John Daugirdas for his review of the phosphate-binding capacity section. This article was researched and written with support from Keryx Biopharmaceuticals, Inc.

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    This article has an online CPE activity available at www.kidney.org/professionals/CRN/ceuMain.cfm

    Support: See Acknowledgments on page 216.

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