Clinical utility of patiromer, sodium zirconium cyclosilicate, and sodium polystyrene sulfonate for the treatment of hyperkalemia: an evidence-based review

Mario V Beccari, Calvin J Meaney, Mario V Beccari, Calvin J Meaney

Abstract

Introduction: Hyperkalemia is a serious medical condition that often manifests in patients with chronic kidney disease and heart failure. Renin-angiotensin-aldosterone system inhibitors are known to improve outcomes in these disease states but can also cause drug-induced hyperkalemia. New therapeutic options exist for managing hyperkalemia in these patients which warrant evidence-based evaluation.

Aim: The objective of this article was to review the efficacy and safety evidence for patiromer, sodium zirconium cyclosilicate (ZS9), and sodium polystyrene sulfonate (SPS) for the treatment of hyperkalemia.

Evidence review: Current treatment options to enhance potassium excretion are SPS and loop diuretics, which are complicated by ambiguous efficacy and known toxicities. Patiromer and ZS9 are new agents designed to address this treatment gap. Both unabsorbable compounds bind potassium in the gastrointestinal (GI) tract to facilitate fecal excretion. The capacity to bind other medications in the GI tract infers high drug-drug interaction potential, which has been demonstrated with patiromer but not yet investigated with ZS9 or SPS. Phase II and III clinical trials of patiromer and ZS9 demonstrated clear evidence of a dose-dependent potassium-lowering effect and the ability to initiate, maintain, or titrate renin-angiotensin-aldosterone system inhibitors. There is limited evidence base for SPS: two small clinical trials indicated potassium reduction in chronic hyperkalemia. All agents may cause adverse GI effects, although they are less frequent with ZS9. Concerns remain for SPS to cause rare GI damage. Electrolyte abnormalities occurred with patiromer and SPS, whereas urinary tract infections, edema, and corrected QT-interval prolongations were reported with ZS9.

Conclusion: Patiromer and ZS9 have improved upon the age-old standard SPS for the treatment of hyperkalemia. Additional research should focus on drug-drug interactions in patients on multiple medications, incidence of rare adverse events, and use in high-risk populations.

Keywords: evidence-based review; hyperkalemia; patiromer; sodium polystyrene sulfonate; sodium zirconium cyclosilicate.

Conflict of interest statement

Disclosure The authors report no actual or potential conflicts of interest in this work.

References

    1. Evans KJ, Greenberg A. Hyperkalemia: a review. J Intensive Care Med. 2005;20(5):272–290.
    1. Weiner ID, Wingo CS. Hyperkalemia: a potential silent killer. J Am Soc Nephrol. 1998;9(8):1535–1543.
    1. Jain N, Kotla S, Little BB, et al. Predictors of hyperkalemia and death in patients with cardiac and renal disease. Am J Cardiol. 2012;109(10):1510–1513.
    1. Palmer BF. Regulation of potassium homeostasis. Clin J Am Soc Nephrol. 2015;10(6):1050–1060.
    1. Salem CB, Badreddine A, Fathallah N, Slim R, Hmouda H. Drug-induced hyperkalemia. Drug Saf. 2014;37(9):677–692.
    1. Palmer BF. Managing hyperkalemia caused by inhibitors of the renin-angiotensin-aldosterone system. N Engl J Med. 2004;351(6):585–592.
    1. Perazella MA. Drug-induced hyperkalemia: old culprits and new offenders. Am J Med. 2000;109(4):307–314.
    1. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;3(1):1–150. No authors listed.
    1. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;128(16):e240–e327.
    1. Emmett M, Hootkins RE, Fine KD, Santa Ana CA, Porter JL, Fordtran JS. Effect of three laxatives and a cation exchange resin on fecal sodium and potassium excretion. Gastroenterology. 1995;108(3):752–760.
    1. Kayexalate (sodium polystyrene sulfonate, USP) [package insert] Bridgewater, NJ: Sanofi-Aventis; 2009.
    1. Cheng ES, Stringer KM, Pegg SP. Colonic necrosis and perforation following oral sodium polystyrene sulfonate (Resonium A/Kayexalate) in a burn patient. Burns. 2002;28(2):189–190.
    1. Gerstman BB, Kirkman R, Platt R. Intestinal necrosis associated with postoperative orally administered sodium polystyrene sulfonate in sorbitol. Am J Kidney Dis. 1992;20(2):159–161.
    1. Harel Z, Harel S, Shah PS, Wald R, Perl J, Bell CM. Gastrointestinal adverse events with sodium polystyrene sulfonate (Kayexalate) use: a systematic review. Am J Med. 2013;126(3):264.e9–e24.
    1. Sterns RH, Rojas M, Bernstein P, Chennupati S. Ion-exchange resins for the treatment of hyperkalemia: are they safe and effective? J Am Soc Nephrol. 2010;21(5):733–735.
    1. Gruy-Kapral C, Emmett M, Santa Ana CA, Porter JL, Fordtran JS, Fine KD. 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):1924–1930.
    1. Watson M, Abbott KC, Yuan CM. Damned if you do, damned if you don’t: potassium binding resins in hyperkalemia. Clin J Am Soc Nephrol. 2010;5(10):1723–1726.
    1. Packham DK, Rasmussen HS, Lavin PT, et al. Sodium zirconium cyclosilicate in hyperkalemia. N Engl J Med. 2015;372(3):222–231.
    1. Weir MR, Bakris GL, Bushinsky DA, et al. Patiromer in patients with kidney disease and hyperkalemia receiving RAAS inhibitors. N Engl J Med. 2015;372(3):211–221.
    1. Veltassa (Patiromer) [package insert] Redwood City, CA: Relypsa; 2015.
    1. Montaperto AG, Gandhi MA, Gashlin LZ, Symoniak MR. Patiromer: a clinical review. Curr Med Res Opin. 2016;32(1):155–164.
    1. Epstein M, Palmer B, Mayo M, et al. Mechanism of action of patiromer for oral suspension: increases fecal K+ excretion in healthy volunteers independent of race. 2015. [Accessed March 3, 2017]. Available from: .
    1. Stavros F, Yang A, Leon A, Nuttall M, Rasmussen HS. Characterization of structure and function of ZS-9, a K+ selective ion trap. PLoS One. 2014;9(12):e114686.
    1. Packham DK, Rasmussen HS, Lavin PT, et al. Sodium zirconium cyclosilicate in hyperkalemia. N Engl J Med. 2015;372(3):222–231.
    1. Kosiborod M, Rasmussen HS, Lavin P, et al. Effect of sodium zirconium cyclosilicate on potassium lowering for 28 days among outpatients with hyperkalemia: the HARMONIZE randomized clinical trial. JAMA. 2014;312(21):2223–2233.
    1. Center for Drug Evaluation and Research Clinical pharmacology and biopharmaceutics review(s) – application number: 205739Orig1s000. 2015. [Accessed February 1, 2016]. Available from: .
    1. US Food and Drug Administration FDA drug safety communication: FDA requires drug interaction studies with potassium-lowering drug Kayexalate (sodium polystyrene sulfonate) 2015. [Accessed February 1, 2016]. Available from: .
    1. Bakris GL, Pitt B, Weir MR, et al. Effect of patiromer on serum potassium level in patients with hyperkalemia and diabetic kidney disease: the AMETHYST-DN randomized clinical trial. JAMA. 2015;314(2):151–161.
    1. Pitt B, Anker SD, Bushinsky DA, Kitzman DW, Zannad F, Huang IZ. Evaluation of the efficacy and safety of RLY5016, a polymeric potassium binder, in a double-blind, placebo-controlled study in patients with chronic heart failure (the PEARL-HF) trial. Eur Heart J. 2011;32(7):820–828.
    1. Bushinsky DA, Williams GH, Pitt B, et al. Patiromer induces rapid and sustained potassium lowering in patients with chronic kidney disease and hyperkalemia. Kidney Int. 2015;88(6):1427–1433.
    1. Pitt B, Bakris GL, Bushinsky DA, et al. Effect of patiromer on reducing serum potassium and preventing recurrent hyperkalaemia in patients with heart failure and chronic kidney disease on RAAS inhibitors. Eur J Heart Fail. 2015;17(10):1057–1065.
    1. Ash SR, Singh B, Lavin PT, Stavros F, Rasmussen HS. A phase 2 study on the treatment of hyperkalemia in patients with chronic kidney disease suggests that the selective potassium trap, ZS-9, is safe and efficient. Kidney Int. 2015;88(2):404–411.
    1. Anker SD, Kosiborod M, Zannad F, et al. Maintenance of serum potassium with sodium zirconium cyclosilicate (ZS-9) in heart failure patients: results from a phase 3 randomized, double-blind, placebo-controlled trial. Eur J Heart Fail. 2015;17(10):1050–1056.
    1. Kosiborod M, Peacock WF, Packham DK. Sodium zirconium cyclosilicate for urgent therapy of severe hyperkalemia. N Engl J Med. 2015;372(16):1577–1578.
    1. Scherr L, Ogden DA, Mead AW, Spritz N, Rubin AL. Management of hyperkalemia with a cation-exchange resin. N Engl J Med. 1961;264(3):115–119.
    1. Nasir K, Ahmad A. 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):455–458.
    1. Lepage L, Dufour AC, Doiron J, 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):2136–2142.
    1. Kjeldsen K. Hypokalemia and sudden cardiac death. Exp Clin Cardiol. 2010;15(4):e96–e99.
    1. Bowling CB, Pitt B, Ahmed MI, et al. Hypokalemia and outcomes in patients with chronic heart failure and chronic kidney disease: findings from propensity-matched studies. Circ Heart Fail. 2010;3(2):253–260.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe