In addition to its potassium-binding ability, sodium zirconium cyclosilicate (SZC) may also increase serum bicarbonate levels in nondialysis chronic kidney disease (CKD) patients with hyperkalemia, according to the authors of an exploratory analysis published in Nephrology Dialysis Transplantation.  

“The SZC-associated increase in serum bicarbonate could provide adjunctive treatment alongside oral sodium bicarbonate for patients with CKD and acidosis, which could enable sodium bicarbonate dose reductions for some patients,” Simon D. Roger, MD, of Renal Research in Gosford, Australia, and colleagues stated.

The investigators conducted post hoc analyses of 3 trials: ZS-003, HARMONIZE, and HARMONIZE-Global, including more than 1200 patients with CKD stage 1 to 5 randomly assigned to SZC (up to 10 g thrice daily) or placebo for 48 hours to correct hyperkalemia, followed by maintenance therapy (SZC up to 15 g once daily or placebo) for up to 29 days.

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In ZS-003, mean serum bicarbonate significantly increased dose dependently by 0.3 to 1.5 mmol/L within 48 hours with SZC 5 to 10 g thrice daily, regardless of CKD stage. Across the trials, mean serum bicarbonate increased by approximately 2 mmol/L within 48 hours with SZC 10 g thrice daily and by 2 to 3 mmol/L during the maintenance phase with SZC 10 g once daily over 29 days. With the highest SZC maintenance doses of 10 g and 15 g once daily, the proportions of patients with serum bicarbonate levels below 22 mmol/L significantly declined from 39.4% at baseline to 4.9% at 29 days in HARMONIZE and from 87.9% to 70.1% in HARMONIZE-Global.

Among SZC-treated patients, increases in serum bicarbonate correlated with decreases in serum urea, supporting the hypothesis that SZC traps ammonium in the gastrointestinal tract independently of its effect on potassium binding, according to the authors. At baseline, only 7% of patients in ZS-003 and HARMONIZE and 16% of patients in HARMONIZE-Global were taking oral sodium bicarbonate.

Acute increases in serum bicarbonate were greater among patients with baseline serum bicarbonate less than 22 mmol/L, Dr Roger’s team noted, suggesting that “SZC does not overcorrect low serum bicarbonate or precipitate alkalosis.”

Edema and hypokalemia are among the known potential adverse effects of SZC.

Disclosure: This clinical trial was supported by AstraZeneca, the makers of sodium zirconium cyclosilicate (Lokelma®). Please see the original reference for a full list of authors’ disclosures.


Roger SD, Spinowitz BS, Lerma EV, et al. Sodium zirconium cyclosilicate increases serum bicarbonate concentrations among patients with hyperkalaemia: exploratory analyses from three randomized, multi-dose, placebo-controlled trials [published online June 26, 2020]. Nephrol Dial Transplant. doi: 10.1093/ndt/gfaa158