Does Lokelma Increase Serum Sodium?
Lokelma (sodium zirconium cyclosilicate) does not significantly increase serum sodium levels despite containing 400 mg of sodium per 5-gram dose, as demonstrated by clinical studies showing no meaningful change in urinary sodium excretion with therapeutic dosing. 1, 2
Mechanism and Sodium Content
- Lokelma binds potassium in exchange for both hydrogen ions (H+) and sodium ions (Na+) throughout the gastrointestinal tract, which theoretically could release sodium for absorption 1
- Each 5-gram dose contains 400 mg of sodium, compared to 1500 mg per 15-gram dose of sodium polystyrene sulfonate 1
- Standard dosing involves 10 g three times daily initially (1200 mg sodium per dose), then 5-15 g once daily for maintenance (400-1200 mg sodium daily) 1
Clinical Evidence on Sodium Balance
- A Phase 1 study specifically evaluating sodium excretion in healthy adults found no significant changes in urinary sodium excretion with either 5 g or 10 g daily dosing (mean changes of -0.93 mmol/24h and -5.47 mmol/24h respectively, both non-significant) 2
- The study demonstrated that despite the sodium content in Lokelma, there was no clinically meaningful systemic sodium absorption or retention 2
- Multiple phase 3 trials with over 750 patients showed no reports of hypernatremia as an adverse event 3, 4, 5
Actual Clinical Concerns
- The primary sodium-related adverse effect is dose-dependent edema, not hypernatremia, occurring in approximately 14% of patients receiving the highest 15-gram daily dose 5
- Edema rates were 2% with placebo, 2% with 5 g, 6% with 10 g, and 14% with 15 g daily dosing, suggesting fluid retention rather than direct sodium elevation 5
- The most common adverse effects are gastrointestinal disorders (constipation, diarrhea, nausea) and hypokalemia, not sodium-related complications 1
Practical Monitoring Recommendations
- Monitor for peripheral edema, particularly when using maintenance doses ≥10 g daily 1, 5
- Routine serum sodium monitoring is not specifically required based on the mechanism of action, though standard electrolyte panels should include sodium 2
- The risk of edema may be more relevant than hypernatremia in patients with heart failure or advanced chronic kidney disease 4
Important Caveat
- While Lokelma does not significantly increase serum sodium, the edema observed suggests some degree of sodium and fluid retention that manifests as volume expansion rather than hypernatremia 5