Calcium Polystyrene Sulfonate and Intestinal Ischemia Risk
Calcium polystyrene sulfonate appears to carry a lower risk of serious gastrointestinal adverse events, including intestinal ischemia, compared to sodium polystyrene sulfonate, though it is not entirely risk-free.
Evidence from Clinical Studies
Comparative Safety Profile
A large nationwide French registry study of 43,771 dialysis patients found that calcium polystyrene sulfonate (CPS) use was not associated with increased risk of adverse gastrointestinal events compared to periods without CPS exposure: incidence rate 8.6 per 1000 person-years on-CPS versus 7.8 per 1000 person-years off-CPS (adjusted HR 0.76,95% CI 0.31-1.80, P=0.52) 1.
In the same study, sodium polystyrene sulfonate (SPS) similarly showed no increased risk in dialysis patients (adjusted HR 0.81,95% CI 0.60-1.09, P=0.17), though this contrasts with other populations 1.
Risk in Non-Dialysis Populations
A population-based Canadian study of 20,020 matched pairs of adults ≥66 years found that sodium polystyrene sulfonate use was associated with nearly double the risk of hospitalization for serious gastrointestinal events within 30 days (HR 1.94,95% CI 1.10-3.41), with intestinal ischemia/thrombosis being the most common type of injury 2.
A systematic review identified 58 cases of gastrointestinal adverse events with sodium polystyrene sulfonate, with 76% involving colonic injury and 62% showing transmural necrosis, resulting in 33% mortality 3.
Documented Cases with Calcium Polystyrene Sulfonate
Serious gastrointestinal complications can occur with calcium polystyrene sulfonate, though reported cases are rare. One case report documented ileum and colon perforation with transmural necrosis following high-dose calcium polystyrene sulfonate (Kalimate) administration in a peritoneal dialysis patient with concurrent peritonitis 4.
The pathology in this case showed basophilic angulated crystals characteristic of polystyrene sulfonate resins, confirming the association 4.
Clinical Guideline Recommendations
Preferred Use of Calcium Formulation
Where available, calcium polystyrene sulfonate should be used instead of sodium polystyrene sulfonate for children with severe hypertension and hyperkalemia, as recommended by KDOQI guidelines 5.
This recommendation is based on avoiding the additional sodium load (100 mg sodium per 100 g powder in sodium polystyrene sulfonate) rather than differential gastrointestinal toxicity 5.
Common Adverse Effects
Both formulations share similar gastrointestinal side effects including constipation (approximately 8%), diarrhea, nausea, and vomiting 6, 7.
Serious adverse effects such as intestinal necrosis occur less commonly with calcium polystyrene sulfonate compared to sodium polystyrene sulfonate with sorbitol 6.
Key Clinical Considerations
Risk Factors and Monitoring
The risk of intestinal injury appears highest in patients with:
Neither formulation should be used for emergency treatment of life-threatening hyperkalemia due to delayed onset of action (several hours) 6, 7.
Safer Alternatives
Newer potassium binders (patiromer or sodium zirconium cyclosilicate) are preferred for chronic hyperkalemia management because they have no reported cases of fatal gastrointestinal injury and faster onset of action (1-7 hours) 7.
For severe hyperkalemia, temporary emergency measures (calcium, insulin/glucose, beta-agonists) should be employed first, followed by polystyrene resins only if newer agents are unavailable 6.
Clinical Bottom Line
While calcium polystyrene sulfonate appears safer than sodium polystyrene sulfonate based on the limited comparative data available, it is not without risk of serious gastrointestinal complications including intestinal ischemia and perforation. The overall incidence of these events is low, but when they occur, mortality is substantial. Clinicians should exercise caution with both formulations, particularly in high-risk patients, and strongly consider newer potassium binders as first-line agents for non-emergent hyperkalemia management 6, 7, 1.