In patients with persistent or recurrent hyperkalemia, daily oral sodium zirconium cyclosilicate (SZC) may keep potassium levels in normal range without substantially compromising concomitant use of renin-angiotensin-aldosterone system inhibitor (RAASi) therapy, according to new study findings published online ahead of print in the Clinical Journal of the American Society of Nephrology.

In a 2-part, open label, phase 3 trial of 751 hyperkalemic patients, 746 achieved normokalemia of 3.5 to 5.0 mmol/L after receiving SZC—which binds and removes potassium via the gastrointestinal tract—at a dosage of 10 g three times daily for up to 72 hours, Bruce S. Spinowitz, MD, of New York-Presbyterian Queens, and colleagues reported. In a subsequent maintenance phase, 466 patients continued with SZC 5 g once daily titrated to maintain normokalemia without dietary or medication restrictions for up to 12 months. The average dose was 7.2 g for a mean 286 days to achieve a mean serum potassium level of 4.7 mmol/L. In all, 88% and 99% of participants achieved serum potassium values less than or equal to 5.1 or 5.5 mmol/L, respectively.

Seventy-four percent of patients had an estimated glomerular filtration rate less than 60 mL/min/1.73m2, and 65% used RAASi. Of the 483 RAASi users at baseline, 87% were able to continue or increase their dose while taking SZC, whereas 11% discontinued therapy. Among 263 nonusers, 14% later initiated RAASi.

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“The results from this study are consistent with prior smaller and shorter clinical studies of SZC, and they further show that SZC use is associated with both rapid correction of hyperkalemia and long-term maintenance of normokalemia up to 12 months,” Dr Spinowitz and his collaborators stated.

Two thirds of patients experienced adverse events such as hypertension, edema, nausea, and urinary tract Infection. Twenty-two percent had a serious event. Hypokalemia—potassium levels less than 3.0 and 3.0 to 3.4 mmol/L—occurred in 9 and 34 patients, respectively. Of 8 deaths, none were considered related to SZC.

“The introduction of safe, effective, and well tolerated potassium binders is not simply a measure to treat hyperkalemia, but it may facilitate more opportunity to optimize RAASi use in patients with CKD and/or cardiovascular disease,” Matthew R. Weir, of the University of Maryland in Baltimore, commented in an accompanying editorial.

The study was funded by ZS Pharma, a company owned by AstraZeneca, which manufactures SZC (Lokelma).

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Weir MR. Therapeutic potential of newer drugs for treating hyperkalemia. Clin J Am Soc Nephrol. (Published online May 20, 2019) doi:10.2215/CJN.04750419

Spinowitz BS, Fishbane S, Pergola PE, et al. Sodium zirconium cyclosilicate among individuals with hyperkalemia: A 12-month phase 3 study. Clin J Am Soc Nephrol. (Published online May 20, 2019) doi: 10.2215/CJN.12651018