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Calcium resonium

Calcium resonium

Guideline 8.1 – Calcium resonium for the management of Hyperkalaemia in the community

We suggest that calcium resonium Is no longer used to treat chronic hyperkalaemia.  (2C)

Rationale (Guideline 8.1)

Calcium polystyrene sulphonate (CPS, Calcium resonium) and sodium polystyrene sulphonate (SPS, Kayexalate) are cation exchange resins that work in the lower GI tract to enhance the elimination of K+ in the faeces. CPS is approved for use in Europe and SPS approved for use in the USA.

Each gram of resin has a theoretical in vitro exchange capacity of approximately 1.3 – 2 mmol of K+, but in vivo, it will be less.1 Resins cause constipation, therefore laxatives are given to accelerate resin transit and to increase K+ excretion in stools.2 Lactulose is an osmotic laxative and is commonly used in the UK. Macrogol 3350 (Laxido®, Movicol®) should be avoided as it contains potassium (46.6mg or 5.4mmol/l per sachet).

SPS was approved by the Food and Drug Administration (FDA) in 1958 on the basis of two small uncontrolled case series undertaken in the 1950’s.3 This approval preceded the Kefauver Harris Drug Amendment (1962) and the European Union EC/65/65 directive (1965) requiring drug manufacturers to prove the effectiveness and safety of their drug.4 Following multiple reports of colonic necrosis and other serious gastrointestinal adverse events (perforation, bleeding), the FDA applied safety recommendations in 2009.

Evidence base for CPS and SPS in chronic hyperkalaemia

Although these resins have been used in clinical practice for decades, there have been only 4 RCTs evaluating SPS to reduce potassium levels and only one of these studies showed a statistically significant reduction after seven days.4 7

Gruy Kapral (1998) reported a placebo-controlled randomised study of SPS in normokalaemic patients with ESRD on HD (n=6) and failed to show any significant reduction in serum K+. The size, design and insufficient baseline data renders this study weak.6

Nasir et al (2014) performed a RCT to compare the efficacy and safety of CPS and SPS in CKD patients (n=97) with hyperkalaemia. Although both drugs lowered serum K+, the study lacked adequate statistical analysis to substantiate the claim of equal efficacy and there was no control arm (i.e. placebo group). Of note, fewer side effects were reported with CPS than SPS.5

Lepage et al (2015) conducted a single centre double blind RCT (n=33) in outpatients with CKD and mild hyperkalaemia (K+ 5.0–5.9 mmol/l) comparing efficacy of SPS 30g daily to placebo for 7 days. This study reported an absolute reduction of serum K+ level of 1.25 mmol/l (p<0.001), but the proportion of patients who achieved normokalaemia did not reach statistical significance (p=0.07).4

Nakayama et al (2018) performed a randomised crossover study (n=20) in pre dialysis patients with hyperkalaemia (K+ > 5 mmol/l). Patients received either SPS or CPS therapy for 4 weeks to compare efficacy of these resins. There was no significant difference in serum K+ from baseline between the two groups, but the authors suggested that CPS may be safer as it did not induce volume overload.7

A Cochrane review (2020) evaluated CPS and SPS in chronic hyperkalaemia and concluded there is insufficient high quality evidence to recommend their use for chronic hyperkalaemia in patients with CKD.8

The APPETIZE study (2024) was a multi-centre randomised, blinded cross-over study to evaluate the palatability of and preference for different potassium binders (SPS, CPS, Patiromer and sodium zirconium cyclosilicate (SZC)) for treating chronic hyperkalaemia.[9]  SZC and Patiromer outperformed SPS and CPS on overall palatability and once daily dosing was also favourable.  In all participating regions, SZC was ranked above Patiromer, SPS and CPS as the most favourable K+-binder.

Considerations when using Calcium resonium (CPS)

Tolerability and the risk of severe gastrointestinal adverse effects limit their long term use.9,10 The risk of gastro intestinal events is enhanced by the concomitant use of sorbitol.10

The availability of novel K+-binders (patiromer and sodium zirconium cyclosilicate) with a stronger evidence base for efficacy and more favourable side-effect profiles have now replaced CPS and SPS in clinical practice. 

References

  1. Chaaban, A., et al., Potassium binders in hemodialysis patients: a friend or foe?Ren Fail, 2013. 35(2): p. 185 8.
  2. Emmett, M., et al., Effect of 3 Laxatives and a Cation Exchange Resin on Fecal Sodium and Potassium Excretion. Gastroenterology, 1995. 108(3): p. 752 760.
  3. Parks, M. and D. Grady, Sodium Polystyrene Sulfonate for Hyperkalemia. JAMA Intern Med, 2019.
  4. Lepage, L., et al., Randomized Clinical Trial of Sodium Polystyrene Sulfonate for the Treatment of Mild Hyperkalemia in CKD. Clin J Am Soc Nephrol, 2015. 10(12): p. 2136 42.
  5. Nasir, K. and A. Ahmad, Treatment of hyperkalemia in patients with chronic kidney disease: a comparison of calcium polystyrene sulphonate and sodium polystyrene sulphonate. J Ayub Med Coll Abbottabad, 2014. 26(4): p. 455 8.
  6. Gruy Kapral, C., et al., Effect of single dose resin cathartic therapy on serum potassium concentration in patients with end stage renal disease. J Am Soc Nephrol, 1998. 9(10): p. 1924 30.
  7. Nakayama, Y., et al., Compared effects of calcium and sodium polystyrene sulfonate on mineral and bone metabolism and volume overload in pre dialysis patients with hyperkalaemia. Clin Exp Nephrol, 2018. 22(1): p. 35 44.
  8. Natale, P., et al., Potassium binders for chronic hyperkalaemia in people with chronic kidney disease. Cochrane Database Syst Rev, 2020. 6(6): p. CD013165.
  9. Wheeler, D.C., et al., Randomised, blinded, cross-over evaluation of the palatability of and preference for different potassium binders in participants with chronic hyperkalaemia in the USA, Canada and Europe: the APPETIZE study. BMJ Open, 2024. 14(2): p. e074954
  10. Noel, J.A., et al., Risk of Hospitalization for Serious Adverse Gastrointestinal Events Associated With Sodium Polystyrene Sulfonate Use in Patients of Advanced Age. JAMA Intern Med, 2019. 179(8): p. 1025 1033.
  11. Laureati, P., et al., Initiation of sodium polystyrene sulphonate and the risk of gastrointestinal adverse events in advanced chronic kidney disease: a nationwide study. Nephrol Dial Transplant, 2020. 35(9): p. 1518 1526.