Potassium Binding for Conservative and Preservative Management of Chronic Kidney Disease

Deborah J. Clegg; Biff F. Palmer


Curr Opin Nephrol Hypertens. 2020;29(1):29-38. 

In This Article

Sodium Zirconium Cyclosilicate

Sodium zirconium cyclosilicate (ZS-9/SZC) is a nonabsorbed microporous compound, which binds K+ throughout the gastrointestinal tract in exchange for Na+.[30] SZC was specifically designed as a high-capacity crystalline lattice structure (sodium zirconium) to trap monovalent cations (K+) as opposed to divalent cations. SZC has a rapid onset of action (within 1 h) when given at 10 g thrice daily for up to 48 h in the acute setting (Table 2). The typical initial maintenance dose is 10 g once daily titrated to achieve the desired K+ concentration. Like patiromer, this drug is effective in lowering plasma K+ concentration in a dose-dependent manner with greater reductions in those with the highest K+ levels.

Phase 2 and 3 studies have investigated the efficacy and safety of SZC for the treatment of hyperkalemia in a wide range of patients, including a high proportion of patients with CKD receiving RAASi therapy (Table 4).[36–39] SZC was associated with rapid lowering of serum K+ concentrations, with significant reductions versus baseline observed 1 h after the first 10-g dose.[37] The long-term efficacy of SZC has been studied for up to 1 year in an open-label study that included patients with CKD and patients receiving RAASi therapy.[38] In a recent report, patients with plasma K+ ≥5.1 mEq/l received SZC 10 g three times daily for 24–72 h until normokalemic, and then those patients who qualified for continuation of the study entered a 12-month or less maintenance phase and received SZC 5 g once daily titrated to maintain normokalemia without dietary or medication restrictions.[39] Of 751 participants, 746 (99%) achieved normokalemia during the correction phase and entered the maintenance phase. Of the 483 patients on RAASi therapy at baseline, 87% continued or had their dose increased while only 11% discontinued therapy. Among 263 RAASi therapy-naïve participants, 14% initiated such therapy.

SZC is generally well tolerated with an incidence of gastrointestinal adverse events similar to placebo. There is a dose-related increase in the incidence of mild-to-moderate edema in patients during maintenance dosing.[40,41] Edema rates are more common in patients treated with the 15 g dose, which is the highest dose used in clinical trials. Hypokalmeia is uncommon and resolves with dose reductions or discontinuation of SZC. The drug is also well tolerated and effective when given on nondialysis days to treat predialysis hyperkalemia.[42]