Sustained potassium control and recurrent hyperkalemia during individualized potassium-guided sodium zirconium cyclosilicate titration in maintenance hemodialysis: a post hoc analysis of a randomized trial

A mean predialysis potassium value at a single visit does not show whether the same patient remains controlled across consecutive months or repeatedly crosses hyperkalemic thresholds. We evaluated sustained patient-level potassium control and recurrent hyperkalemia during individualized potassium-guided sodium zirconium cyclosilicate (SZC) therapy on non-dialysis days. This exploratory post hoc analysis used data from a previously reported single-center, open-label randomized trial of 116 patients with chronic hyperkalemia (58 per group). The primary outcome was sustained response during months 3–6, which required all four scheduled predialysis potassium measurements after the long interdialytic interval to be available, at least three of the four values to be within 4.0–5.0 mmol/L, and no unplanned hemodialysis triggered by potassium ≥ 6.5 mmol/L during the evaluation period. Missing measurements were classified as nonresponse. Adjusted risk ratios (aRRs) were estimated using modified Poisson regression with robust standard errors. The primary outcome occurred in 25/58 (43.1%) SZC-treated participants and 8/58 (13.8%) controls (aRR 3.02, 95% confidence interval [CI] 1.49–6.14). Sustained response within 4.0–5.5 mmol/L occurred in 38/58 (65.5%) and 22/58 (37.9%), respectively (aRR 1.74, 95% CI 1.19–2.54). At least two scheduled potassium values ≥ 5.5 mmol/L occurred in 11/58 (19.0%) and 36/58 (62.1%) (aRR 0.31, 95% CI 0.18–0.55). The adjusted incidence rate ratio for visits with potassium ≥ 5.5 mmol/L was 0.36 (95% CI 0.24–0.54). Complete-case and conservative extreme-case missing-data analyses were directionally consistent with the main analysis. Individualized potassium-guided SZC therapy was associated with a higher probability of meeting the sustained biochemical potassium-control criterion at scheduled monthly measurements and with fewer recurrent biochemical hyperkalemic excursions. Clinical outcomes were not evaluated in the present analysis; therefore, the observed biochemical improvements should not be interpreted as evidence of clinical benefit. Chinese Clinical Trial Registry, ChiCTR2600119050. Registered on 14 February 2026; retrospectively registered.