Efficacy and safety of sodium zirconium cyclosilicate on non-dialysis days for long-term management of chronic hyperkalemia in maintenance hemodialysis: a single-center, prospective, open-label, randomized controlled trial.

purposeTo evaluate the efficacy and safety of oral sodium zirconium cyclosilicate (SZC) administered on non-dialysis days for the long-term management of chronic hyperkalemia in patients undergoing maintenance hemodialysis (MHD).

methodsThis single-center, prospective, open-label, parallel-group randomized controlled trial enrolled 116 MHD patients with chronic hyperkalemia and randomly assigned them 1:1 to an SZC group or a control group (58 per group). Both groups received routine hemodialysis and standardized dietary counseling. The SZC group additionally received oral SZC on non-dialysis days, with dose adjustment according to pre-dialysis serum potassium after the long inter-dialytic interval (LIDI). The total observation period was 9 months, including 6 months of treatment and 3 months of post-withdrawal follow-up after discontinuation of study SZC. The primary endpoint was the between-group difference in pre-dialysis serum potassium after LIDI at month 6. Repeated potassium measurements were analyzed using a linear mixed-effects model, with complete-case, multiple-imputation, and conservative missing-not-at-random sensitivity analyses.

resultsBaseline characteristics were generally balanced. The group-by-time interaction was significant (P < 0.001), indicating different potassium trajectories over time. At month 6, the SZC group had a lower pre-dialysis serum potassium level after LIDI than the control group, with a model-estimated mean difference of - 0.363 mmol/L (95% CI - 0.542 to - 0.184). Sensitivity analysis yielded consistent results. During the 6-month treatment period, the frequency of target-range potassium measurements (4.0-5.0 mmol/L) was higher in the SZC group (IRR 1.88, 95% CI 1.476-2.392). Exploratory secondary clinical outcomes, including hyperkalemia-related unplanned hemodialysis, RAASi discontinuation burden, and cardiovascular hospitalizations, were lower in the SZC group, but the small event counts and open-label design preclude definitive clinical conclusions. No obvious within-group changes over time were observed in calcium, magnesium, albumin, hemoglobin, dry weight, or inter-dialytic weight gain-related indices. Five patients (8.6%) in the SZC group experienced mild hypokalemia (3.0-3.5 mmol/L), and four patients (6.9%) experienced constipation; no severe hypokalemia (< 3.0 mmol/L) was observed.

conclusionUnder the conditions of this study, oral SZC on non-dialysis days produced a modest but statistically significant reduction in pre-dialysis serum potassium after LIDI and was generally tolerated. The exploratory clinical-event findings are hypothesis-generating and require confirmation in larger blinded multicenter trials.

trial registrationChinese Clinical Trial Registry, ChiCTR2600119050. Registered February 14, 2026, retrospectively registered. https://www.chictr.org.cn .