Faculty Opinions recommendation of Sodium zirconium cyclosilicate in hyperkalemia.

Abstract Background and Aims Hyperkalemia (HK) is a potentially life-threatening condition, in patients with chronic kidney disease (CKD) and congestive heart failure (CHF). The majority of patients affected with CKD or CHF, must be treated with inhibitors of renin angiotensin aldosterone system (RAASi) and mineralocorticoid receptor antagonists (MRAs). However, the treatments previously mentioned, increase the risk of HK episodes, which is the main cause of RAASi and MRAs downtitration or discontinuation, representing an undesirable clinical scenario, given that the patients are at high risk of be deprived of their nephroprotective effect and cardio-renal benefits The aim of the study is: to analyze if, in patients with HK, CKD and CHF treated with RAASi and/or MRA, serum potassium (sK) reduction by Sodium zirconium cyclosilicate (SZC) treatment is non-inferior to RAASi and/or MRAs discontinuation or downtitration. Method Results The study will demonstrate results on serum electrolytes, renal function, albuminuria, KDQoL questionnaire and changes in relative overhydration (multifrequency bioimpedance -BCM Fresenius-) Conclusion The KEEP ON study will define the ability of SZC to facilitate the use of RAAS-I and / or MRA in patients with HK and cardiorenal syndrome allowing the maintenance of the medications recommended by international guidelines for the treatment of CHF at different degrees of CKD while maintaining the potential cardio-renal and nephroprotective benefit.

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Sodium Zirconium Cyclosilicate among Individuals with Hyperkalemia

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.12651018 ◽

2019 ◽

Vol 14 (6) ◽

pp. 798-809 ◽

Cited By ~ 34

Author(s):

Bruce S. Spinowitz ◽

Steven Fishbane ◽

Pablo E. Pergola ◽

Simon D. Roger ◽

Edgar V. Lerma ◽

...

Keyword(s):

Adverse Events ◽

Confidence Interval ◽

Serum Potassium ◽

Maintenance Phase ◽

Renin Angiotensin Aldosterone System ◽

Once Daily ◽

Renin Angiotensin ◽

Sodium Zirconium ◽

Sodium Zirconium Cyclosilicate ◽

Correction Phase

Background and objectivesOral sodium zirconium cyclosilicate (formerly ZS-9) binds and removes potassium via the gastrointestinal tract. Sodium zirconium cyclosilicate–associated restoration and maintenance of normokalemia and adverse events were evaluated in a two-part, open label, phase 3 trial.Design, setting, participants, & measurementsIn the correction phase, adult outpatients with plasma potassium ≥5.1 mmol/L (i-STAT Point-of-Care) received sodium zirconium cyclosilicate 10 g three times daily for 24–72 hours until normokalemic (potassium =3.5–5.0 mmol/L). Qualifying participants entered the ≤12-month maintenance phase and received sodium zirconium cyclosilicate 5 g once daily titrated to maintain normokalemia without dietary or medication restrictions. Prespecified primary end points were restoration of normal serum potassium values (3.5–5.0 mmol/L) during the correction phase and maintenance of serum potassium ≤5.1 mmol/L during the maintenance phase. Adverse events were assessed throughout.ResultsOf 751 participants, 746 (99%) achieved normokalemia during the correction phase (mean serum potassium =4.8 mmol/L; 95% confidence interval, 4.7 to 4.8) and entered the maintenance phase; 466 (63%) participants completed the 12-month trial. Participants were predominantly white, men, and age ≥65 years old; 74% had an eGFR<60 ml/min per 1.73 m2, and 65% used renin-angiotensin-aldosterone system inhibitors. Mean time on sodium zirconium cyclosilicate was 286 days. Mean daily sodium zirconium cyclosilicate dose was 7.2 g (SD=2.6). Over months 3–12, mean serum potassium was 4.7 mmol/L (95% confidence interval, 4.6 to 4.7); mean serum potassium values ≤5.1 and ≤5.5 mmol/L were achieved by 88% and 99% of participants, respectively. Of 483 renin-angiotensin-aldosterone system inhibitor users at baseline, 87% continued or had their dose increased; 11% discontinued. Among 263 renin-angiotensin-aldosterone system inhibitor–naïve participants, 14% initiated renin-angiotensin-aldosterone system inhibitor therapy. Overall, 489 (66%) participants experienced adverse events during the maintenance phase, and 22% experienced a serious adverse event. Of eight (1%) deaths, none were considered related to sodium zirconium cyclosilicate. Nine (1%) and 34 (5%) participants experienced serum potassium <3.0 and 3.0–3.4 mmol/L, respectively.ConclusionsAfter achieving normokalemia, individualized once daily sodium zirconium cyclosilicate was associated with maintenance of normokalemia without substantial renin-angiotensin-aldosterone system inhibitor changes for ≤12 months.

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