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Potential New Agents for the Management of Hyperkalemia

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Abstract

Hyperkalemia is a common electrolyte disturbance with multiple potential etiologies. It is usually observed in the setting of reduced renal function. Mild to moderate hyperkalemia is usually asymptomatic, but is associated with poor prognosis. When severe, hyperkalemia may cause serious acute cardiac arrhythmias and conduction abnormalities, and may result in sudden death. The rising prevalence of conditions associated with hyperkalemia (heart failure, chronic kidney disease, and diabetes) and broad use of renin-angiotensin-aldosterone system (RAAS) inhibitors and mineralocorticoid receptor antagonists (MRAs), which improve patient outcomes but increase the risk of hyperkalemia, have led to a significant rise in hyperkalemia-related hospitalizations and deaths. Current non-invasive therapies for hyperkalemia either do not remove excess potassium or have poor efficacy and tolerability. There is a clear need for safer, more effective potassium-lowering therapies suitable for both acute and chronic settings. Patiromer sorbitex calcium and sodium zirconium cyclosilicate (ZS-9) are two new potassium-lowering compounds currently in development. Although they have not yet been approved by the US FDA, both have demonstrated efficacy and safety in recent trials. Patiromer sorbitex calcium is a polymer resin and sorbitol complex that binds potassium in exchange for calcium; ZS-9, a non-absorbed, highly selective inorganic cation exchanger, traps potassium in exchange for sodium and hydrogen. This review discusses the merits of both novel drugs and how they may help optimize the future management of patients with hyperkalemia.

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Acknowledgments

The authors received no remuneration for the preparation of this review.

The authors would like to thank Drs. Regina Burris and Mark Rocco, Xelay Acumen, Inc., for medical writing support, which was funded by ZS Pharma.

DP reports having received travel grants and honoraria from ZS Pharma and being an investigator on the 003 and HARMONIZE trials. MK reports having received consulting honoraria and travel support for investigator and advisory board meetings from ZS Pharma, and being an investigator for the HARMONIZE trial.

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Authors and Affiliations

  1. The Melbourne Renal Research Group, Department of Medicine, University of Melbourne, 73 Pine St., Reservoir, Melbourne, VIC, 3073, Australia

    David K. Packham

  2. Department of Nephrology, Royal Melbourne Hospital, Melbourne, VIC, Australia

    David K. Packham

  3. Department of Cardiology, Saint Luke’s Mid America Heart Institute, Kansas City, MO, USA

    Mikhail Kosiborod

  4. Department of Medicine, University of Missouri–Kansas City, Kansas City, MO, USA

    Mikhail Kosiborod

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  1. David K. Packham
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Correspondence to David K. Packham.

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Packham, D.K., Kosiborod, M. Potential New Agents for the Management of Hyperkalemia. Am J Cardiovasc Drugs 16, 19–31 (2016). https://doi.org/10.1007/s40256-015-0130-7

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