Sodium zirconium cyclosilicate for the management of chronic hyperkalemia in kidney disease, a novel agent

ABSTRACT

Introduction

Hyperkalemia is a common finding in patients with advanced kidney disease for multiple reasons. Renin-Angiotensin-Aldosterone-System Inhibitors (RAASi) that are indicated for slowing down progression of kidney disease are often associated with hyperkalemia which becomes a limiting factor in their use and titration to the maximum dose. Having a safe, effective, tolerable, and affordable potassium binder can help optimize RAAS inhibition in the setting of kidney disease.

Areas covered

Although sodium polystyrene sulfonate has been a mainstay of acute management of hyperkalemia for decades, evidence regarding its efficacy is limited, and its chronic use is not routinely recommended for concerns regarding toxicity. The concern of gastrointestinal (GI) adverse effects with sodium polystyrene sulfonate has spurred the development of alternatives. Sodium zirconium cyclosilicate (SZC) is a promising agent that selectively binds potassium in the gut and eliminates it, while being safe for chronic use based on 1 year of data. Even though we do not have head-to-head studies among the three currently available binders, SZC stands out in rapidity of onset and efficacy.

Expert opinion

In this review, we summarize the general management of hyperkalemia, including new agents. We review the pre-clinical and clinical data relating to sodium zirconium cyclosilicate.

KEYWORDS:

• Hyperkalemia
• Chronic Kidney Disease (CKD)
• End Stage Kidney Disease (ESKD)
• Sodium Zirconium Cyclosilicate (SZC)
• Patiromer Calcium
• Sodium Polystyrene Sulfonate (SPS)
• Randomized Clinical Trial (Rct)
• End Of Treatment (EOT)

Article highlights

Hyperkalemia can be a life-threatening disorder associated with kidney disease, that is often asymptomatic. It also limits the optimization of RAASi.

Sodium Polystyrene Sulfonate (SPS) has limited data for its use acutely and is generally not used chronically due to GI side effects (colonic perforation) and poor tolerability.

Dietary potassium restriction is often not practical and can also limit eating healthy foods, which is often high in potassium. Sodium zirconium cyclosilicate (SZC) is one of the two new agents that bind potassium in the GI tract. It has unique pharmacology, earlier onset of action, and excellent tolerability with limited drug–drug interactions (DDI).

There is a potential for sodium absorption with each 5-gm dose of SZC associated with a maximum of 400 mg of sodium exposure. The volume status should be monitored, and appropriate adjustments made including dietary adjustments and use of diuretics. Otherwise, the adverse effect profile was very acceptable.

Acknowledgments

The authors would like to acknowledge Ms. Christina Lopez and the UCLA CORE Kidney Health Program.

Declaration of interest

A Rastogi serves as a member of the speaker’s bureau and advisory board and a consultant for AstraZeneca and Relypsa. He was also the Principal Investigator on the DIALIZE study. N Nobakht was a sub-investigator for the DIALIZE study. M Kamgar serves as a member if the speaker’s bureau for AstraZeneca and Lokelma. Dr. Kamgar was a sub-investigator for the DIALIZE study. E Lerma serves as a member on the advisory board for AstraZeneca. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer of this manuscript discloses serving as a consultant and having stock options with Relypsa/vifor; serving as a consultant for Astra Zeneca; serving as a consultant Bayer; serving as a consultant and owning stock options with Sarfez: serving as a consultant for Phasebio and serving as a consultant and owning stock options with KBP Pharmaceuticals. The reviewer also discloses owning US Patent 9,931,412-site specific delivery of Eplerenone to the myocardium. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.