Background <p>Hyperkalemia is a common complication of chronic kidney disease (CKD) that often requires urgent dialysis and increases healthcare costs. Daily sodium zirconium cyclosilicate (SZC) is a safe and effective treatment for the control of serum potassium levels in CKD patients. We studied the efficacy and safety of intermittent SZC therapy for the prevention of hyperkalemia in CKD patients.</p> Methods <p>In a retrospective study, we analyzed patients in the Hospital Authority Clinical Data Analysis and Reporting System (CDARS) receiving sodium zirconium cyclosilicate (Lokelma^®) therapy once to thrice weekly for at least 3 months from January 2021 to June 2023. Outcome measures included plasma potassium levels, hyperkalemia episodes, hospital admissions, and renal function changes, which were compared to the 6 months period before the initiation of SZC treatment.</p> Results <p>We studied 36 adult CKD patients. SZC treatment significantly reduced plasma potassium levels from 5.10 (inter-quartile range [IQR] 4.91–5.40) to 4.73 (IQR 4.50–5.10) mmol/l (<i>p</i> = 0.0003). The median incidence of any hyperkalemia reduced from 5.0 (IQR 2.0–8.0) to 1.9 (IQR 0.0–4.7) episode per patient-year (<i>p</i> = 0.0001), and the incidence of urgent treatment for hyperkalemia decreased from 2.0 (IQR 0.0–4.0) to 0.0 (IQR 0.0–1.5) episode per patient-year (<i>p</i> = 0.007). The number of emergency room attendance and hospitalization were not significantly reduced.</p> Conclusion <p>Intermittent SZC treatment may help prevent hyperkalemia in CKD patients. Further research is necessary to ascertain if this benefit translates into improvements in hard clinical outcomes.</p> Clinical trial number <p>Not applicable.</p>