Supplementary Material for: Effect of sodium zirconium cyclosilicate approval on the management of acute hyperkalemia in Japan: Interrupted time series analysis

Introduction: The impact of the new potassium binder sodium zirconium cyclosilicate (SZC) on the real-world management of acute hyperkalemia remains unknown. The aim of this study was to evaluate changes in treatment strategies and clinical outcomes for acute hyperkalemia following the approval of SZC in Japan. Methods: We conducted a retrospective cohort study using the RWD database, a nationwide electronic medical record and claims database in Japan, including adult patients who were hospitalized with hyperkalemia (serum potassium ≥5.5 mmol/L) between April 2015 and December 2024. Using an interrupted time series analysis, we evaluated changes in outcomes following SZC approval in April 2020. The post-approval period was stratified to distinguish the effects of the coronavirus disease 2019 (COVID-19) pandemic. The primary outcome was the monthly proportion of patients receiving renal replacement therapy (RRT). Secondary outcomes included in-hospital mortality, intensive care unit (ICU) admission, and maintenance hemodialysis initiation. Results: Overall, 38,540 hospitalizations were included. While no significant immediate change in RRT use occurred upon SZC approval, a significant decreasing trend was subsequently observed (slope change, -0.7% per month; 95% confidence interval (CI), -1.2 to -0.1%). This downward trend in RRT use was highly pronounced after the COVID-19 pandemic ended. A significant decreasing trend in ICU admissions was observed in the post-pandemic period (slope change, -4.2% per month; 95% CI, -6.6 to -1.7%). Trends of in-hospital mortality and maintenance hemodialysis initiation did not significantly change. Conclusions: Following SZC approval, a decreasing trend in the use of RRT for acute hyperkalemia was observed, along with a post-pandemic decrease in ICU admissions. These trends were not accompanied by an observable increase in in-hospital mortality or initiation of maintenance hemodialysis.