Inclusion Criteria:  Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol Provision of signed and dated, written ICF prior to any mandatory study specific procedures, sampling, and analyses Must be ≥ 18 years of age, at the time of signing the ICF. For participants < 20 years of age and enrolled in Japan, a written informed consent should be obtained from the participant and his or her legally acceptable representative Receiving hemodialysis (or hemodiafiltration) 3 times a week for treatment of ESRD for ≥ 4 months before enrollment Must have hemodialysis access consisting of an arteriovenous fistula, arteriovenous graft, or tunneled (permanent) catheter which is expected to remain in place for the entire duration of the study At least 2 out of 3 pre-dialysis S K ≥ 5.5 mmol/L after the LIDI during screening Negative pregnancy test for female participants of childbearing potential Female participants must be 1 year postmenopausal, surgically sterile, or using one highly effective form of birth control (defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly). They should have been stable on their chosen method of birth control for a minimum of 3 months before entering the study and willing to remain on the birth control until 12 weeks after the last dose  Exclusion Criteria:  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) Presence of cardiac arrhythmias or conduction defects that require immediate treatment Participants who have a pacemaker or implantable cardiac defibrillator Any medical condition, including active, clinically significant infection or liver disease, that in the opinion of the investigator or sponsor may pose a safety risk to a participant in this study, confound safety or efficacy assessment and jeopardize the quality of the data, or interfere with study participation, or any other restrictions or contraindications in the local prescribing information for SZC History of QT prolongation associated with other medications that required discontinuation of that medication Congenital long QT syndrome QTcF > 550 msec Symptomatic or uncontrolled AF despite treatment, or asymptomatic sustained ventricular tachycardia Treated with SPS (eg, Kayexalate, Resonium), CPS (Resonium Calcium), patiromer (Veltassa), or SZC (Lokelma) within 7 days before screening Participation in another clinical study with an investigational product administered within one month before screening Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site) Judgment by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements Previous randomization in the present study Females who are pregnant (confirmed with positive pregnancy test or a uterine ultrasound if pregnancy test result is questionable), breastfeeding, or planning to become pregnant during the study Known hypersensitivity or previous anaphylaxis to SZC or to components thereof Scheduled date for living donor kidney transplant