Effects of Sodium Zirconium Cyclosilicate on Volume Status in Maintenance Hemodialysis: Post Hoc Analysis from the DIALIZE-Outcomes Trial.

BACKGROUND

The Effect of Sodium Zirconium Cyclosilicate on Arrythmia-Related Cardiovascular Outcomes in Participants on Chronic Hemodialysis with Recurrent Hyperkalemia (DIALIZE-Outcomes) trial evaluated the effect of sodium zirconium cyclosilicate (SZC) on arrhythmia-related cardiovascular outcomes among patients receiving maintenance hemodialysis. The study was terminated early because of a low event rate and high treatment discontinuation. As SZC exchanges sodium for potassium, volume expansion from increased sodium absorption is a potential adverse effect. This post hoc analysis evaluated the effects of SZC versus placebo on volume status.

METHODS

Adults receiving maintenance hemodialysis with predialysis hyperkalemia (serum potassium ≥5.5 mmol/L) were randomized 1:1 to SZC (starting dose 5 g once daily on non-dialysis days, titrated as needed; N=1349) or placebo (N=1341). Indicators of volume status included: adverse events (AEs) related to volume status, antihypertensive medication use, change in predialysis blood pressure, and change in interdialytic weight gain (IDWG).

RESULTS

For the 2690 randomized participants, 62% were male, mean (SD) age was 56.1 (13.4) years, predialysis weight was 75.3 (19.8) kg, and dialysis vintage was 5.9 (5.3) years. In the SZC and placebo groups, there were similar proportions of participants with AEs of edema (5% versus 5%), heart failure (5% versus 5%), and hypertension (9% versus 8%). Mean (SD) changes from baseline to end of follow-up were similar between SZC and placebo for predialysis systolic (-2.1 [24.3] versus -2.2 [22.2] mm Hg) and diastolic (-0.9 [15.0] versus -0.8 [14.2] mm Hg) blood pressure, and IDWG (+0.2 [2.6] versus +0.1 [2.4] kg). The number of antihypertensive medications used was similar between SZC and placebo at baseline (85% versus 83%) and during follow-up (88% versus 86%).

CONCLUSIONS

In this post hoc analysis of a large trial of patients with hyperkalemia receiving hemodialysis, there was no clinical evidence of volume changes with SZC. This supports the use of SZC as hyperkalemia treatment among patients receiving hemodialysis-a population at high risk for hypervolemia.