Long-term safety and efficacy of sodium zirconium cyclosilicate for hyperkalaemia in patients with mild/moderate versus severe/end-stage chronic kidney disease: comparative results from an open-label, Phase 3 study

Abstract

Background Sodium zirconium cyclosilicate (SZC; formerly ZS-9) is a selective potassium (K+) binder for the treatment of adults with hyperkalaemia. This post hoc analysis of an open-label, single-arm trial (NCT02163499) compared SZC efficacy and safety >12 months among outpatients with hyperkalaemia and Stages 4 and 5 chronic kidney disease (CKD) versus those with Stages 1–3 CKD. Methods Adults with serum K+ ≥5.1 mmol/L (measured by point-of-care i-STAT device) received SZC 10 g three times daily for 24–72 h until normokalaemia (i-STAT K+ 3.5–5.0 mmol/L) was achieved [correction phase (CP)], followed by once daily SZC 5 g for ≤12 months [maintenance phase (MP)]. Here, patients were stratified by baseline estimated glomerular filtration rate (eGFR <30 or ≥30 mL/min/1.73 m2). Study endpoints included percent achieving normokalaemia during CP and MP, mean serum K+ and bicarbonate during MP, and adverse events (AEs). Results Of 751 patients enrolled, 289 (39%), 453 (60%) and 9 (1%) had baseline eGFR values of <30, ≥30 mL/min/1.73 m2 or missing, respectively. During the CP, 82% of patients achieved normokalaemia in both eGFR subgroups within 24 h, and 100 and 95% with baseline eGFR <30 and ≥30 mL/min/1.73 m2, respectively, within 72 h. Corresponding proportions with normokalaemia during the MP were 82 and 90% at Day 365, respectively. Mean serum K+ reduction from baseline during the CP was sustained throughout the MP and serum bicarbonate increased. AEs during the MP were more common in the eGFR <30 ≥30 mL/min/1.73 m2 subgroup. Conclusions SZC corrects hyperkalaemia and maintains normokalaemia among outpatients regardless of the CKD stage.

Analysing the impact of a guideline for the use of new potassium binders for treatment of chronic hyperkalaemia to maximise inhibition of renin–angiotensin–aldosterone system (RAAS) within the general nephrology clinic?

“…Outpatient studies evaluating the use of these newer potassium binding agents within selected chronic kidney disease patient groups experiencing hyperkalaemia has demonstrated the correction and maintenance of normokalaemia [17] as well as the ability to maintain or increase the dose of RAAS inhibition in a signi cant proportion of patients [18]. These ndings were predominantly in those patients with moderate to severe CKD, where 75% were CKD stage 3 or 4, and this mirrors the patient group reported on within this general nephrology clinic.…”

New Treatment Options for Hyperkalemia in Patients with Chronic Kidney Disease

“…Interestingly, a post hoc analysis of ZS-005 focused on the study of the subgroups of patients with CKD. Furthermore, in this case, SZC use was associated with a significant reduction in serum K + levels in the long-term maintenance phase, in a similar manner even when patients were stratified via baseline-estimated glomerular filtration rate (i.e., eGFR < 30 or > 30 mL/min) [73].…”

Effects and Safety of a Novel Oral Potassium-Lowering Drug-Sodium Zirconium Cyclosilicate for the Treatment of Hyperkalemia: a Systematic Review and Meta-Analysis

“…The safety of SZC is the main issues of concern. The current research reported the side effects of SZC mainly included gastrointestinal disorders (including nausea, vomiting, diarrhea and constipation), cardiac disorders, urinary tract infection, edema and hypokalemia [20][21][22][23][24][25][26][27][28][29][30]33]. In our meta-analysis, of all adverse events mentioned above, SZC only increased the risk of edema compared with placebo.…”

“…Kosiborod et al found SZC reduced and maintained normal potassium for up to 4 weeks in patients with CKD, heart failure, and diabetes [24]. A study of hyperkalemia patients with renal insufficiency found that during SZC treatment, the average sK + levels decreased from 5.7 to 4.8 mmol/L in patients with eGFR < 30 mL/min/1.73 m2 and from 5.6 to 4.7 mmol/L in those with eGFR ≥30 mL/min/1.73 m2 at day 365 [33]. They also pointed the proportions of patients who reached normal potassium during the maintenance period were 82 and 90% for the eGFR < 30 and ≥ 30 mL/min/1.73 m2 group at day 365, respectively.…”