What are common phosphate binders used in clinical practice?

Common Phosphate Binders in Clinical Practice

The most commonly used phosphate binders are calcium-based agents (calcium carbonate and calcium acetate), non-calcium binders (sevelamer and lanthanum carbonate), and newer iron-based binders (ferric citrate and sucroferric oxyhydroxide). 1

Calcium-Based Phosphate Binders

Calcium Carbonate

• Contains 40% elemental calcium and is the most widely prescribed phosphate binder due to low cost and proven efficacy 2
• Effectively lowers serum phosphorus but causes more hypercalcemic events compared to other binders 1
• Associated with increased risk of vascular calcification when used long-term, particularly when total calcium intake exceeds 2,000 mg/day 3
• Gastrointestinal side effects are lowest among all phosphate binders 1

Calcium Acetate

• Contains 25% elemental calcium and is FDA-approved for phosphate reduction in end-stage renal disease 4
• More effective gram-for-gram at lowering serum phosphorus compared to calcium carbonate (relative phosphate-binding coefficient of 1.0 vs calcium carbonate) 1, 5
• Causes fewer hypercalcemic episodes than calcium carbonate at equivalent phosphate-binding doses 1, 2
• Starting dose is 2 capsules (667 mg each) with each meal, titrated every 2-3 weeks; most patients require 3-4 capsules per meal 4

Critical calcium threshold: Total elemental calcium from all sources (diet + binders + dialysate) must not exceed 2,000 mg/day, with calcium from binders alone ideally under 1,500 mg/day. 3

Non-Calcium, Non-Aluminum Binders

Sevelamer (Hydrochloride or Carbonate)

• The only calcium- and aluminum-free binder with proven efficacy and safety in children, studied in 47 pediatric patients 1
• Relative phosphate-binding coefficient of 0.75 compared to calcium carbonate (less potent gram-for-gram) 5
• Attenuates progression of arterial calcifications compared to calcium-based binders in adults with CKD stages 3-5 1
• The Renagel In New Dialysis Patients trial showed significant mortality reduction in incident dialysis patients receiving sevelamer for median 44 months 1
• Additional benefit: decreases LDL cholesterol by 34% 1
• Caveat: Higher incidence of metabolic acidosis compared to calcium-based binders 1
• Large pill burden and high cost limit wider use 6

Lanthanum Carbonate

• Calcium- and aluminum-free binder with high phosphate affinity and minimal intestinal absorption 1
• Relative phosphate-binding coefficient of 2.0 (twice as potent as calcium carbonate gram-for-gram) 5
• Controls plasma phosphate well and induces less adynamic bone disease than calcium carbonate 1
• Concerns about tissue accumulation in liver, kidney, and bone exist, though 6-year safety data show acceptable profile 6
• No long-term safety data in children available 1

Iron-Based Phosphate Binders

Sucroferric Oxyhydroxide

• Consists of polynuclear iron(III)-oxyhydroxide with sucrose and starches 7
• As effective as sevelamer in reducing phosphatemia with similar safety profile 7
• Major advantage: Lower pill burden compared to other binders 8, 7
• Minimal iron absorption without inducing toxicity 7

Ferric Citrate

• Dual benefit: phosphate binding plus improvement in iron parameters 8
• Newer agent with growing evidence base 9

Magnesium-Based Binders

• Magnesium carbonate (anhydrous) has relative phosphate-binding coefficient of 1.7; hydrated form has coefficient of 1.3 5
• Provides equivalent phosphorus control to calcium carbonate 1
• Major limitation: Requires decreased magnesium concentration in dialysate, difficult in centralized dialysate delivery systems 1
• No long-term safety and efficacy studies available; use justified only if all other compounds fail 1

Aluminum-Based Binders (Historical/Limited Use)

• Aluminum hydroxide (coefficient 1.5) and aluminum carbonate (coefficient 1.9) are highly efficient 5
• Should be avoided except as short-term rescue therapy (maximum 4 weeks) for severe hyperphosphatemia >7.0 mg/dL due to proven toxicity 1, 3

Clinical Decision Algorithm

When selecting a phosphate binder:

1. First-line for most patients: Calcium-based binders (acetate preferred over carbonate for better efficacy and less hypercalcemia) 1, 2

2. Switch to or add non-calcium binders when:

   • Hypercalcemia present (serum calcium >10.2 mg/dL) 3
   • Total calcium intake approaching 2,000 mg/day 3
   • Calcium-phosphorus product >55 mg²/dL² 3
   • Existing vascular or soft-tissue calcification 3
   • Low PTH (<150 pg/mL on two consecutive measurements) 3

3. Combination therapy: Add sevelamer to calcium-based binder for persistent hyperphosphatemia (>5.5 mg/dL) despite monotherapy, allowing better phosphorus control while limiting calcium load 3

Common Pitfalls

• Non-adherence is the biggest challenge to phosphate binder efficacy 8
• Calcium citrate should be avoided in CKD patients as it enhances calcium absorption more than other calcium salts 2
• Phosphate binders must be taken 10-15 minutes before or during meals to maximize phosphate binding and minimize free calcium absorption 2
• Dietary phosphate restriction alone is insufficient; urinary phosphorus excretion does not decrease and may increase by 50% over 2 years despite low-phosphorus diet 1