Review ArticleAn Update on Phosphate Binders: A Dietitian's Perspective
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.
References (56)
- et al.
Cardiovascular calcification in patients with end-stage renal disease: a century-old phenomenon
Kidney Int Suppl
(2002) - et al.
Effect of calcium-based versus non-calcium-based phosphate binders on mortality in patients with chronic kidney disease: an updated systematic review and meta-analysis
Lancet
(2013) - et al.
Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients
Kidney Int
(2002) - et al.
Effects of sevelamer and calcium on coronary artery calcification in patients new to hemodialysis
Kidney Int
(2005) - et al.
Mortality effect of coronary calcification and phosphate binder choice in incident hemodialysis patients
Kidney Int
(2007) - et al.
RenaGel, a nonabsorbed calcium- and aluminum-free phosphate binder lowers serum phosphorus and serum parathyroid hormone. The RenaGel Study Group
Kidney Int
(1999) - et al.
A comparison of the calcium-free phosphate binder sevelamer hydrochloride with calcium acetate in the treatment of hyperphosphatemia in hemodialysis patients
Am J Kidney Dis
(1999) - et al.
A multicenter study on the effects of lanthanum carbonate (Fosrenol) and calcium carbonate on renal bone disease in dialysis patients
Kidney Int Suppl
(2003) - et al.
Comparison of dietary phosphate absorption after single doses of lanthanum carbonate and sevelamer carbonate in healthy volunteers: a balance study
Am J Kidney Dis
(2011) - et al.
A phase III study of the efficacy and safety of a novel iron-based phosphate binder in dialysis patients
Kidney Int
(2014)
Dose-response and efficacy of ferric citrate to treat hyperphosphatemia in hemodialysis patients: a short-term randomized trial
Am J Kidney Dis
The phosphate binder ferric citrate and mineral metabolism and inflammatory markers in maintenance dialysis patients: results from prespecified analyses of a randomized clinical trial
Am J Kidney Dis
Salivary glands: a new player in phosphorus metabolism
J Ren Nutr
Mineral metabolism, mortality, and morbidity in maintenance hemodialysis
J Am Soc Nephrol
Calcium, phosphate, and parathyroid hormone levels in combination and as a function of dialysis duration predict mortality: evidence for the complexity of the association between mineral metabolism and outcomes
J Am Soc Nephrol
The effect of aluminium hydroxide on calcium, phosphorus and aluminium balances and the plasma parathyroid hormone in patients with chronic renal failure
Clin Sci
Factors associated with mortality in patients new to haemodialysis
Nephrol Dial Transplant
Meta-analysis comparing sevelamer and calcium-based phosphate binders on cardiovascular calcification in hemodialysis patients
Nephron Clin Pract
Fosrenol [Prescribing Information]
Phoslyra [Prescribing Information]
Renvela [Prescribing Information]
Randomized controlled trial of bixalomer versus sevelamer hydrochloride in hemodialysis patients with hyperphosphatemia
Ther Apher Dial
Effect of chitosan chewing gum on reducing serum phosphorus in hemodialysis patients: a multi-center, randomized, double-blind, placebo-controlled trial
BMC Nephrol
Velphoro [Prescribing Information]
Auryxia [Prescribing Information]
A randomized, double-blind, placebo-controlled trial of niacinamide for reduction of phosphorus in hemodialysis patients
Clin J Am Soc Nephrol
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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.