What is the difference between aluminum hydroxide (Lowphos) and Sevelamer in treating hyperphosphatemia in patients with chronic kidney disease (CKD), and which one is preferred?

Aluminum Hydroxide (Lowphos) vs Sevelamer in Hyperphosphatemia

Sevelamer is strongly preferred over aluminum hydroxide (Lowphos) for treating hyperphosphatemia in CKD patients, as aluminum-based binders should only be used as short-term rescue therapy (maximum 4 weeks, one course only) due to significant toxicity risks including aluminum accumulation, bone disease, and inferior phosphate control. 1

Key Differences Between the Two Agents

Aluminum Hydroxide (Lowphos)

• Highly restricted use: Should only be considered when serum phosphorus >7.0 mg/dL as short-term therapy for 4 weeks maximum, one course only 1
• Significant toxicity: Causes aluminum accumulation, aluminum-related bone disease, and is associated with worse outcomes 2
• Inferior efficacy: Less effective than calcium carbonate (and by extension, other modern binders) for phosphate control 2
• Impairs bone healing: Prevents improvement of secondary hyperparathyroidism compared to other binders 2

Sevelamer

• First-line option: Can be used as primary therapy in dialysis patients (CKD Stage 5) 1
• No calcium load: Does not cause hypercalcemia, unlike calcium-based binders 3, 4
• Cardiovascular benefits: May reduce all-cause mortality (RR 0.53) compared to calcium-based binders in dialysis patients 5
• Additional benefits: Reduces LDL cholesterol by 13-24% 6, 4
• Equivalent phosphate control: Achieves similar phosphate reduction as calcium-based binders without hypercalcemia risk 6, 4

Clinical Algorithm for Phosphate Binder Selection

For CKD Stages 3-4 (Non-Dialysis)

Target phosphorus: 2.7-4.6 mg/dL 1, 3

1. First step: Dietary phosphorus restriction to 800-1,000 mg/day 1
2. If phosphorus >4.6 mg/dL despite diet:
   • Start calcium-based binders OR sevelamer 1
   • Never use aluminum hydroxide in this population 1

For CKD Stage 5 (Dialysis Patients)

Target phosphorus: 3.5-5.5 mg/dL 1, 3

Choose sevelamer as first-line when:

• Hypercalcemia present (serum calcium >10.2 mg/dL) 1, 3
• PTH <150 pg/mL on two consecutive measurements 1, 3
• Severe vascular or soft-tissue calcifications present 1, 3
• Need to restrict calcium intake 3
• Patient age >65 years (signal for harm with calcium binders) 1

Aluminum hydroxide only if:

• Phosphorus >7.0 mg/dL AND
• Failed all other binders AND
• Use for maximum 4 weeks, one course only 1
• Must replace with other binders after 4 weeks 1

Critical Safety Considerations

Why Aluminum is Dangerous

• Causes aluminum accumulation even at "recommended" doses of 30 mg/kg/day 2
• Develops aluminum-related bone disease 2
• Maintains higher phosphorus levels than alternatives 2
• Prevents skeletal improvement from secondary hyperparathyroidism 2

Sevelamer Safety Profile

• Main side effect: constipation (RR 6.92 compared to placebo) 5
• Does not increase hypercalcemia risk (5% vs 22% with calcium acetate) 4
• May reduce mortality by approximately 50% compared to calcium-based binders in dialysis patients 5

Combination Therapy Approach

• If phosphorus remains >5.5 mg/dL on monotherapy, combine sevelamer with calcium-based binders 1, 3
• Ensure total elemental calcium intake (diet + binders) does not exceed 2,000 mg/day 1, 3
• Calcium from binders alone should not exceed 1,500 mg/day 1

Common Pitfall to Avoid

Never use aluminum hydroxide as chronic therapy or first-line treatment. The historical use of aluminum binders has been abandoned due to unacceptable toxicity, and current guidelines restrict it to extreme rescue situations only for very short duration. 1, 2