What are the differences between Renvela (sevelamer carbonate), Fosrenol (lanthanum carbonate), and Velphoro (sucroferric oxyhydroxide) for treating hyperphosphatemia in patients with chronic kidney disease (CKD) or end-stage renal disease (ESRD)?

Phosphate Binder Comparison: Renvela, Fosrenol, and Velphoro

Direct Recommendation

For patients with CKD stages 3-5D requiring non-calcium phosphate binders, all three agents (Renvela/sevelamer, Fosrenol/lanthanum, and Velphoro/sucroferric oxyhydroxide) are effective alternatives to calcium-based binders, with the choice primarily driven by pill burden tolerance, gastrointestinal side effects, cost considerations, and specific clinical scenarios such as hypercalcemia or vascular calcification. 1

When to Use Non-Calcium Phosphate Binders

Restrict calcium-based phosphate binders and preferentially use non-calcium alternatives in the following situations: 1

• Hypercalcemia (corrected calcium >10.2 mg/dL) 1
• PTH levels persistently <150 pg/mL on consecutive measurements 1
• Severe vascular or soft-tissue calcifications present 1
• Progressive coronary or aortic calcification on imaging 1
• Adynamic bone disease 2
• Total elemental calcium intake approaching or exceeding 2,000 mg/day 1

Key Differences Between the Three Agents

Renvela (Sevelamer Carbonate)

Mechanism and efficacy:

• Polymeric phosphate binder that works through ion exchange without systemic absorption 3, 4
• Effective at reducing serum phosphate across CKD stages 3-5D 1
• Retains high phosphate-binding affinity over wide pH range 4

Unique advantages:

• Lowers LDL cholesterol and total cholesterol by 15-30% through bile acid binding 3, 4
• May attenuate progression of vascular calcification compared to calcium-based binders 3, 5
• No metal accumulation concerns 3

Important limitations:

• Can worsen metabolic acidosis, particularly problematic in non-dialyzed CKD patients 3, 4
• High pill burden (typically 6-12 tablets daily) affecting adherence 4, 6
• Gastrointestinal side effects (bloating, constipation, nausea) common 4, 6
• Less efficient phosphate binding in acidic gastric environment 4

Fosrenol (Lanthanum Carbonate)

Mechanism and efficacy:

• Trivalent cation that directly binds phosphate with high affinity 3, 4
• Potent and selective phosphate binding maintained across pH 3-7 4
• Effective phosphate reduction comparable to or better than sevelamer 4, 7

Unique advantages:

• Lower pill burden than sevelamer (typically 3-6 tablets daily), improving adherence 4, 6, 7
• Does not bind bile acids, avoiding lipid or fat-soluble vitamin interference 4
• Does not contribute to metabolic acidosis 4
• Chewable formulation may improve palatability for some patients 6

Important limitations:

• Minimal systemic absorption occurs with tissue deposition in bone, liver, and gastric mucosa 3, 4
• Long-term safety data regarding lanthanum accumulation still evolving, though no clinical toxicity demonstrated in trials up to 6 years 3, 4, 6
• Gastrointestinal side effects (nausea, vomiting, constipation) occur but generally mild 4, 6
• More expensive than calcium-based binders but cost-effective compared to sevelamer in some analyses 7

Velphoro (Sucroferric Oxyhydroxide)

Mechanism and efficacy:

• Iron-based phosphate binder using polynuclear iron(III)-oxyhydroxide 6
• Highly effective phosphate binding with low pill burden 6
• Comparable or superior efficacy to other non-calcium binders 6

Unique advantages:

• Lowest pill burden of all phosphate binders (typically 2-3 tablets daily) 6
• May provide supplemental iron, potentially beneficial in dialysis patients with iron deficiency 6
• Does not contribute to metabolic acidosis 6
• Effective across wide pH range 6

Important limitations:

• Can cause black discoloration of stool (benign but may alarm patients) 6
• Gastrointestinal side effects (diarrhea, discolored feces, nausea) common 6
• Potential for iron overload in patients with adequate iron stores requires monitoring 6
• Limited long-term safety data compared to sevelamer and lanthanum 6
• Most expensive option among phosphate binders 6

Clinical Decision Algorithm

Step 1: Confirm indication for phosphate binder therapy

• Only treat progressively or persistently elevated phosphate, not normal levels 1, 8
• Target phosphate 3.5-5.5 mg/dL in dialysis patients 1, 2
• Target phosphate ≤4.6 mg/dL in CKD stages 3-4 1, 8

Step 2: Assess calcium status and vascular calcification

• If hypercalcemia, low PTH, or documented vascular calcification present: avoid calcium-based binders entirely 1
• If normocalcemic without calcification: calcium-based binders remain acceptable first-line option, but restrict total elemental calcium to <1,500 mg/day from binders 1

Step 3: Select non-calcium binder based on patient-specific factors

Choose Velphoro if:

• Pill burden is the primary adherence barrier 6
• Patient has concurrent iron deficiency anemia 6
• Cost is not prohibitive 6

Choose Fosrenol if:

• Moderate pill burden reduction needed 4, 6, 7
• Patient has metabolic acidosis (avoid sevelamer) 4
• Patient has dyslipidemia already well-controlled (sevelamer benefit not needed) 4
• Cost-effectiveness is priority over sevelamer 7

Choose Renvela if:

• Patient has significant dyslipidemia requiring LDL reduction 3, 4, 5
• Cardiovascular calcification progression is primary concern 3, 5
• Patient has adequate acid-base status 3, 4
• Long-term safety profile is priority (most extensive data) 3

Step 4: Monitor and adjust

• Check phosphate monthly after initiation or dose changes 1, 2
• Monitor calcium, PTH, and acid-base status together, not in isolation 1, 2
• If single agent inadequate, combine non-calcium binders or add limited calcium-based binder 1

Critical Pitfalls to Avoid

Do not treat normal phosphate levels with binders in non-dialysis CKD patients - this increases coronary calcification without benefit 1, 8

Do not ignore metabolic acidosis when prescribing sevelamer - it worsens acidemia particularly in CKD stages 3-4 not yet on dialysis 3, 4

Do not exceed 2,000 mg/day total elemental calcium intake when combining dietary calcium with any calcium-based binders 1

Do not base treatment decisions on single elevated phosphate values - use serial measurements with calcium and PTH assessed together 1, 2

Do not assume all phosphate binders are interchangeable - calcium-based binders specifically increase vascular calcification risk compared to non-calcium alternatives 1