A Study to Test Whether ZS (Sodium Zirconium Cyclosilicate) Can Reduce the Incidence of Increased Blood Potassium Levels Among Dialized Patients.

Inclusion Criteria: 1. Provision of informed consent prior to any study specific procedures 2. Female or male aged ≥ 18 years at screening Visit 1. For patients aged \<20 years and enrolled in Japan, a written informed consent should be obtained from the patient and his or her legally acceptable representative. 3. Receiving hemodialysis (or hemodiafiltration) 3 times a week for treatment of endstage renal disease (ESRD) for at least 3 months before randomization. 4. Patients must have hemodialysis access consisting of an arteriovenous fistula, AV graft, or tunneled (permanent) catheter which is expected to remain in place for the entire duration of the study. 5. Pre-dialysis serum K \>5.4 mmol/L after long inter-dialytic interval and \>5.0 mmol/L after one short inter-dialytic interval during screening (as assessed by central lab). 6. Prescribed dialysate K concentration ≤ 3 mmol/L during screening 7. Sustained Qb ≥200 ml/min and spKt/V ≥1.2 (or URR ≥ 63) on stable hemodialysis/hemodiafltration prescription during screening with prescription (time, dialyzer, blood flow \[Qb\], dialysate flow rate \[Qd\] and bicarbonate concentration) expected to remain unchanged during study 8. Heparin dose (if used) must be stable during screening and expected to be stable during the study 9. Subjects must be receiving dietary counseling appropriate for ESRD patients treated with hemodialysis/hemodiafiltration as per local guidelines, which includes dietary potassium restriction. Exclusion Criteria: 1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca, including ZS Pharma staff and/or staff at the study site) 2. Hemoglobin \<9 g/dL on screening (as assessed on Visit 1) 3. Lack of compliance with hemodialysis prescription (both number and duration of treatments) during the two-week period preceding screening (100% compliance required) 4. Patients treated with sodium polystyrene sulfonate (SPS, Kayexalate, Resonium), calcium polystyrene sulfonate (CPS, Resonium calcium) or patiromer (Veltassa) within 7 days before screening or anticipated in requiring any of these agents during the study 5. Myocardial infarction, acute coronary syndrome, stroke, seizure or a thrombotic/thromboembolic event (e.g., deep vein thrombosis or pulmonary embolism, but excluding vascular access thrombosis) within 12 weeks prior to randomization 6. Laboratory diagnosis of hypokalemia (K \< 3.5 mmol/L), hypocalcemia (Ca \< 8.2 mg/dL; for Japan hypocalcemia is defined as albumin-corrected Ca \< 8.0 mg/dL), hypomagnesemia (Mg \< 1.7 mg/dL) or severe acidosis (serum bicarbonate 16 mEq/L or less) in the 4 weeks preceding randomization 7. Pseudohyperkalemia secondary to hemolyzed blood specimen (this situation is not considered screening failure, sampling or full screening can be postponed to a later time as applicable). 8. Severe leukocytosis (\>20× 10\^9/L) or thrombocytosis (≥450 × 10\^9/L) during screening 9. Polycythemia (Hb \>14 g/dL) during screening 10. Diagnosis of rhabdomyolysis during the 4 weeks preceding randomization 11. Patients treated with lactulose, xifaxan (rifaximin) or other non-absorbed antibiotics for hyperammonemia within 7 days prior to the first dose of study drug 12. Patients unable to take oral ZS drug mix 13. Scheduled date for living donor kidney transplant 14. Patients with a life expectancy of less than 6 months 15. Female patients who are pregnant or breastfeeding 16. Females of childbearing potential, unless using contraception as detailed in the protocol or sexual abstinence. 17. Known hypersensitivity or previous anaphylaxis to ZS or to components thereof 18. Participation in another clinical study with an investigational product during the last 1 month before screening 19. Any medical condition, including active, clinically significant infection, that in the opinion of the investigator or Sponsor may pose a safety risk to a patient in this study, which may confound safety or efficacy assessment and jeopardize the quality of the data, or may interfere with study participation 20. Presence of cardiac arrhythmias or conduction defects that require immediate treatment 21. History of alcohol or drug abuse within 2 years prior to randomization 22. Previous randomization in the present study