Does Sevelamer Lower Blood Calcium and Phosphate?
Sevelamer effectively lowers serum phosphate levels without raising serum calcium, and in fact typically reduces calcium levels compared to calcium-based phosphate binders, making it the preferred choice when hypercalcemia or excessive calcium load is a concern. 1, 2
Mechanism and Effect on Phosphate
Sevelamer is a non-absorbed polymer containing multiple protonated amines that bind dietary phosphate in the gastrointestinal tract through ionic and hydrogen bonding, thereby reducing phosphate absorption and lowering serum phosphate concentrations 2
In randomized controlled trials, sevelamer achieved control of serum phosphorus levels similar to calcium-based phosphate binders, meeting K/DOQI recommended targets 1
Mean serum phosphate reductions range from 2.1 to 2.9 mg/dL during treatment, with significant decreases in calcium-phosphate product (range -16.3 to -23.4 mg²/dL²) 3
European studies demonstrated reduction of phosphate from 7.4 ± 1.4 mg/dL to 5.4 ± 0.8 mg/dL (p < 0.001) over six weeks, with 95% of patients achieving calcium-phosphate product less than 60 mg²/dL² 4
Effect on Calcium Levels
Sevelamer does NOT raise serum calcium because it contains no calcium 1, 2
Sevelamer generally reduces serum calcium levels to a greater extent than calcium-based binders and is associated with significantly fewer hypercalcemic episodes 1, 5
In prospective randomized trials, the calcium-treated group experienced more hypercalcemic episodes and more PTH suppression compared to the sevelamer group 1
When calcium-based binders are discontinued and sevelamer initiated, serum calcium typically declines (e.g., from 9.2 ± 0.5 to 8.7 mg/dL), while ionized calcium remains stable 4
Clinical Advantages Over Calcium-Based Binders
The K/DOQI guidelines strongly recommend adding sevelamer when patients require more than 2,000 mg/day of elemental calcium from calcium-based binders to decrease total calcium intake 1
In patients with baseline vascular calcification, sevelamer prevented progression of aortic and coronary artery calcification, while calcium-based binders showed significant progression 1
Sevelamer reduces LDL cholesterol by 15-31% and total cholesterol significantly compared to calcium-based binders, providing additional cardiovascular benefit 1, 2
Total calcium intake (including from binders) can be reduced by 81% when switching from calcium-based binders to sevelamer 4
Specific Clinical Scenarios for Sevelamer Use
Use sevelamer in patients with hypercalcemia, elevated calcium-phosphorus product, or severe vascular calcification where calcium-based binders are contraindicated 1, 6
Consider sevelamer in patients with low-turnover bone disease who cannot incorporate calcium loads, predisposing them to extraskeletal calcification 1
The American Journal of Kidney Diseases suggests sevelamer may reduce mortality in incident dialysis patients based on trial data 6
Important Caveats
Sevelamer should be used in combination with vitamin D metabolites to jointly control hyperphosphatemia and hyperparathyroidism, as sevelamer alone may increase PTH levels 3
Gastrointestinal side effects (flatulence, nausea, indigestion) occur in approximately 70% of patients but are typically mild 7
Sevelamer binds bile acids and may reduce absorption of fat-soluble vitamins (A, D, K), requiring monitoring 2
The drug requires 4-7 tablets daily on average, which may impact adherence, though this is fewer than some calcium-based regimens 6, 7
Monitor serum phosphorus every 2-4 weeks during titration, then monthly once stable, and check intact PTH every 3 months 6