Dose Effect Post Hoc Analysis of DIALYZE Study Data

Results of the DIALIZE trial (NCT03303521) demonstrated that sodium zirconium cyclosilicate (SZC) reduced predialysis serum potassium after the long interdialytic interval. Further, SZC is well tolerated in hemodialysis patients with hyperkalemia. Bruce Spinowitz, MD, and colleagues conducted a post hoc analysis to examine the dose effect of SZC on predialysis body weight, blood pressure, and ultrafiltration rate during dialysis. They reported results during the NKF Spring Clinical Meetings in a presentation titled Dose Effect Analysis of Sodium Zirconium Cyclosilicate (SZC) in Hyperkalemic Hemodialysis Patients in the DIALYZE Study.

The DIALYZE study cohort included 196 patients who were randomized 1:1 to placebo (n=99) or SZC (n=97); the safety analysis included 195 of the 196 patients. The starting dose was 5 g once daily on non-dialysis days for a 4-week dose titration (titrated in 5 g increments to 15 g maximum) to achieve predialysis potassium 4.0 to 5.0 mmol/L, and a 4-week stable dose evaluation phase (SZC 0, 5, 10, or 15 g).

The post hoc analysis examined change from baseline (visit 4, day 1) to the end of treatment (visit 15, day 57) in interdialytic weight gain, diastolic blood pressure, systolic blood pressure, and ultrafiltration rate, stratified by final SZC dose in the dose titration phase. Dialysis ultrafiltration rate was calculated as actual ultrafiltration (mL)/dialysis duration (h)/ predialysis weight (kg).

During the dose evaluation phase, 38, 41, and 17 patients received SZC 5, 10, and 15 g, respectively. There was no consistent pattern in changes from baseline in interdialytic weight gain, diastolic blood pressure, systolic blood pressure, and ultrafiltration rate. There was no relationship between changes and SZC dose.

“Findings of no increases in blood pressure, interdialytic weight gain, or ultrafiltration rate with higher SZC doses suggest that dose adjustments based on patients’ serum potassium resulted in comparable safety,” the researchers said.

Source: Spinowitz B, Fishbane S, McCafferty K, et al. Dose effect analysis of sodium zirconium cyclosilicate (SZC) in hyperkalemia hemodialysis patients in the DIALYZE study. Abstract of a presentation at the National Kidney Foundation 2020 Spring Clinical Meetings; abstract #260.