A Prospective, Randomized, Open-Label, Cross-Over Study of Lokelma to Control Interdialytic Hyperkalemia

Inclusion Criteria: * Provision of informed consent prior to any study-specific procedures * Female or male aged above 18 years * Patients with ESRD receiving hemodialysis three times per week for a minimum of 3 months * Patients must have two (2) pre-dialysis K+ measurements between 5.1 and 6.5 mEq/L by Piccolo POCT following the long dialytic "weekends" (i.e., on two consecutive Mondays for patients on a Monday-Wednesday-Friday dialysis schedule or on two consecutive Tuesdays for patients on a Tuesday-Thursday-Saturday dialysis schedule) during screening, before insertion of the cardiac loop recorder. * Female participants must be 1 year post-menopausal, 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 1 month before entering the study and willing to remain on the birth control until 4 weeks after the last dose. Exclusion Criteria: \- Exclusion Criteria Related to the Underlying Condition: * Patients with a QTc(f) \> 550 msec and/or Congenital long QT syndrome * Patients with a Haemoglobin \< 9 g/dl. * Patients with 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 subject in this study, which may confound safety or efficacy assessment and jeopardize the quality of the data, or may interfere with study participation. * Patient receiving peritoneal or home hemodialysis * Patient receiving hemodialysis via a tunneled inferior vena cava (IVC) catheter and known central stenosis of access extremity * Patient receiving outpatient hemodialysis for \< 3 months * Patient receiving outpatient hemodialysis for prolonged Acute Kidney Injury (AKI) and considered by the site Principal Investigator (PI) likely to achieve renal recovery within 6 months Note: Patients receiving out-patient hemodialysis for AKI for longer than 6 months with no demonstrable renal clearance can be screened for study participation. * Patient currently receiving a 1.0 K+, 3.0 K+ dialysate bath and unwilling to convert to a 2.0 K+/2.5 Ca++ dialysate bath * Subject unwilling to convert from a 2.0 K+ dialysate bath to a 3.0 K+ dialysate bath * Two or more pre-dialysis K+ of \< 5.1 or \> 6.5 mEq/L measured by Piccolo POCT after the long dialytic "weekends" during screening Note: If one of the two screening pre-dialysis K+ levels is between 4.6 to 5.0 mEq/L or 6.6 to 7.0 mEq/L, the patient can undergo an additional whole blood Piccolo POCT K+ measurement. Patients who fail the third whole blood Piccolo POCT K+ measurement will be considered ineligible for study participation. Note: Screen failures can be re-screened once to confirm eligibility in the study. * Any documented whole blood Piccolo POCT K+ measurement that falls below 4.6 mEq/L or exceeds 7.0 mEq/l during the screening period * Current use of a medication for treatment of hyperkalemia (e.g., Patiromer). * Note: If a medication for treatment of hyperkalemia is stopped prior to or after the consenting process, the subject will undergo a one week washout prior to the first whole blood Piccolo POCT K+ measurement. Exclusion Criteria Related to Other Medical Conditions and Treatments: * Anticipated life expectancy of 3 months duration * Development of atrial fibrillation requiring hospitalization, medical therapy, anticoagulation, or cardioversion during study pre-screening or screening period * Patient with a known placement of a dual or single chamber pacemaker * Patient with an automatic implantable cardiac defibrillator (AICD) * Patient with a LINQ implanted cardiac loop recorder with less than 6 months of battery life. * Current use of amiodarone or other anti-arrhythmic therapy. Note: Patients on such medications must undergo a two week washout prior to the first whole blood Piccolo POCT K+ measurement. * Known history of cardiac arrhythmias due to prolonged QT syndrome * Subject unwilling to receive an implanted LINQ cardiac loop recorder (unless 6 months are remaining in their previously implanted device). * Known active drug abuse * Positive hepatitis C polymerase chain reaction (PCR) test with active viral deoxyribonucleic acid (DNA) shedding or chronic active hepatitis B as evidenced by detectable surface antigen from standard of care routine dialysis labs. Note: Patients with negative PCR DNA testing for either hepatitis B or C will be allowed to participate in the study. * Known to have tested positive for human immunodeficiency virus (HIV) from standard of care routine dialysis labs. * For women only: currently pregnant (confirmed with positive pregnancy test) or breastfeeding. * Patients with known and/or active severe constipation, bowel obstruction or impaction, including abnormal post-operative bowel motility disorders or diabetic gastroparesis Exclusion Criteria Related to the Investigational Product (IP): * Known hypersensitivity to sodium zirconium cyclosilicate (Lokelmaâ). Other/General Exclusion Criteria: * Previous randomization in the present study. Note: Screen failures can be re-screened once to confirm eligibility in the study. * Participation in another interventional (non-observational) clinical study within 4 weeks prior to enrollment in the present study