Sodium zirconium cyclosilicate increases serum bicarbonate concentrations among patients with hyperkalaemia: exploratory analyses from three randomized, multi-dose, placebo-controlled trials. Issue 5 (26th June 2020)

• Record Type: Journal Article
• Authors: Roger, Simon D; Spinowitz, Bruce S; Lerma, Edgar V; Fishbane, Steven; Ash, Stephen R; Martins, Julian G; Quinn, Carol Moreno; Packham, David K
• Is Part Of: Nephrology dialysis transplantation. Volume 36:Issue 5(2021)
• Page Start: 871
• Page End: 883
• Publication Date: 2020-06-26
• Subjects: hyperkalaemia -- potassium -- serum bicarbonate -- serum urea -- sodium zirconium cyclosilicate; Nephrology -- Periodicals; Hemodialysis -- Periodicals; Kidneys -- Transplantation -- Periodicals; Hemodialysis; Kidneys -- Transplantation; Nephrology; Periodicals; 616.61
• DOI: 10.1093/ndt/gfaa158
• Languages: English
• ISSNs: 0931-0509

Abstract

Abstract: Background: Sodium zirconium cyclosilicate (SZC) binds potassium and ammonium in the gastrointestinal tract. In addition to serum potassium reduction, Phase 2 trial data have shown increased serum bicarbonate with SZC, which may be clinically beneficial because maintaining serum bicarbonate ≥22 mmol/L preserves kidney function. This exploratory analysis examined serum bicarbonate and urea, and urine pH data from three SZC randomized, placebo-controlled Phase 3 studies among patients with hyperkalaemia [ZS-003 ( n = 753), HARMONIZE ( n = 258) and HARMONIZE-Global ( n = 267)]. Methods: In all studies, patients received ≤10 g SZC 3 times daily (TID) for 48 h to correct hyperkalaemia, followed by randomization to maintenance therapy with SZC once daily (QD) versus placebo for ≤29 days among those achieving normokalaemia. Results: Significant dose-dependent mean serum bicarbonate increases from baseline of 0.3 to 1.5 mmol/L occurred within 48 h of SZC TID in ZS-003 (all P < 0.05), which occurred regardless of chronic kidney disease (CKD) stage. Similar acute increases in HARMONIZE and HARMONIZE-Global were maintained over 29 days. With highest SZC maintenance doses, patient proportions with serum bicarbonate <22 mmol/L fell from 39.4% at baseline to 4.9% at 29 days (P = 0.005) in HARMONIZE and from 87.9% to 70.1%, (P = 0.006) in HARMONIZE-Global. Path analyses demonstrated that serum urea decreases (but not serum potassium or urine pH changes) were associated with SZC effects on serum bicarbonate. Conclusions: SZC increased serum bicarbonate concentrations and reduced patient proportions with serum bicarbonate <22 mmol/L, likely due to SZC-binding of gastrointestinal ammonium. These SZC-induced serum bicarbonate increases occurred regardless of CKD stage and were sustained during ongoing maintenance therapy.