Lokelma (sodium zirconium cyclosilicate) / AstraZeneca - LARVOL DELTA

Sodium Zirconium Cyclosilicate for Management of Hyperkalemia During Spironolactone Optimization in Patients with Heart Failure. (PubMed, J Am Coll Cardiol) - P4 | "In participants with HFrEF and hyperkalemia, SZC led to large improvements in the percentage of participants with normokalemia while on optimal spironolactone dose, and reduced risk of hyperkalaemia and down-titration/discontinuation of spironolactone. Although underpowered for clinical outcomes, more participants had HF events with SZC than placebo, which should be factored into the clinical decision making."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure

Sodium Zirconium Cyclosilicate and MRA Optimization in Heart Failure With Reduced Ejection Fraction and Hyperkalemia: Main Results From REALIZE-K Randomized Controlled Trial (AHA 2024) - P4 | "Background: Mineralocorticoid receptor antagonists (MRAs) improve outcomes in patients (pts) with heart failure and reduced ejection fraction (HFrEF) but are underused due to hyperkalemia (HK) risk.Hypothesis: We tested if sodium zirconium cyclosilicate (SZC) can enable optimization of the MRA spironolactone (SPL) in pts with HFrEF and HK. REALIZE-K (NCT04676646) was a prospective, double-blind, placebo-controlled, randomized-withdrawal trial in pts with HFrEF (NYHA Class II–IV; left ventricular ejection fraction ≤40%), optimal HF therapy (except MRAs), and prevalent or incident MRA-induced HK. In pts with HFrEF and HK, SZC led to large improvements in the percentage of pts with NK while on optimal dose of SPL. Imbalance in HF events was observed in SZC vs PBO but was limited to those with very high natriuretic peptide levels at baseline."

Clinical • Late-breaking abstract • Cardiovascular • Congestive Heart Failure • Heart Failure

Hyperkalemia-Related Hospitalization Associated with Short-Term vs. Long-Term Outpatient SZC Therapy Among RAASi Users: The GALVANIZE Outcome study (AHA 2024) - "Sodium zirconium cyclosilicate (SZC) is used to treat HK, but the impact of duration of SZC on healthcare resource utilization (HRU) in RAASi users is unknown... Among patients with RAASi and SZC therapy use, long-term SZC use was associated with significantly lower rates of HK-related HRU compared to matched patients with short-term SZC use.Funding: AstraZeneca"

Clinical • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Heart Failure • Hypertension • Metabolic Disorders • Nephrology

Comparison of Sodium Zirconium Cyclosilicate to Calcium Polystyrene Sulfonate for Acute Hyperkalemia Among Hospitalized Elderly Patients. (PubMed, Cureus) - "Conclusions Compared with CPS, SZC might reduce serum potassium more among hospitalized elderly patients with hyperkalemia. Further studies are warranted to determine the role of SZC for acute hyperkalemia in acute care settings."

Journal • Chronic Kidney Disease • Nephrology • Renal Disease

Potassium of 8? It May Be Okay to Wait (KIDNEY WEEK 2024) - "We report an unusual cause of severe hyperkalemia, resistant to therapy, in a patient with suspected tumor lysis syndrome.Case Description: A 69-year old man undergoing chemotherapy with Bendamustine and Rituximab for Chronic Lymphocytic Leukemia (CLL) was admitted for possible tumor lysis syndrome...He was started on IV fluids and allopurinol for TLS and given calcium gluconate, albuterol, Lasix, and insulin for hyperkalemia. His renal function improved to a Cr of 1.5 mg/dL and BUN of 18 mg/dL; however, his hyperkalemia persisted, ranging from 5.5 to 6.5 mmol/L, for which he was repeatedly shifted and started on sodium zirconium cyclosilicate TID...Hyperkalemia in CLL is thought to be due to lysis of white cells during the centrifugation step necessary for measuring plasma or serum K. Blood gas analyzers use capillary or venous whole blood samples and do not require centrifugation. Timely recognition of pseudo-hyperkalemia is required to avoid unnecessary and..."

Acute Kidney Injury • Chronic Lymphocytic Leukemia • Endocrine Disorders • Hematological Disorders • Hematological Malignancies • Leukemia • Metabolic Disorders • Nephrology • Oncology • Renal Disease

Intermittent Sodium Zirconium Cyclosilicate for the Prevention of Hyperkalemia in CKD (KIDNEY WEEK 2024) - "Intermittent low dose sodium zirconium cyclosilicate is effective for potassium control and enhances the management of hyperkalemia in CKD."

Chronic Kidney Disease

Effectiveness, Safety, and Treatment Patterns of Sodium Zirconium Cyclosilicate (SZC) for Hyperkalemia (HK) in China: Final Results of the Actualize Study (KIDNEY WEEK 2024) - "SZC was effective and safe in treating HK in CKD pts, and can be considered as standard treatment for acute and chronic HK in China."

Clinical • Chronic Kidney Disease • Nephrology • Renal Disease

Cost-effectiveness of sodium zirconium cyclosilicate for the treatment of hyperkalemia in patients with chronic kidney disease or heart failure in Spain. (PubMed, Nefrologia (Engl Ed)) - "SZC is a cost-effective alternative for the treatment of HK in patients with CKD or HF, taking into account the reference efficiency values commonly used in Spain."

Cost effectiveness • HEOR • Journal • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Heart Failure • Nephrology • Renal Disease

Mineralocorticoid Receptor Antagonist (MRA) Use Patterns following Potassium Binder Initiation: Insights from the DEMONSTRATE Database (KIDNEY WEEK 2024) - "This study aims to investigate the treatment pattern of MRA following initiation of treatment with potassium binders. From the DEMONSTRATE database (six regions in mid-Sweden) patients with at least one pharmacy dispensation of first (sodium polystyrene sulfonate, SPS) or second-generation (patiromer or sodium zirconium cyclosilicate, SZC) potassium binders between 2005 and 2022 were selected, prescriptions were estimated and treatment episodes were established. 2,146 and 280 patients were treated with MRA and initiated first and second-generation K+ binders.The second-generation users tended to have a higher comorbidity profile. MRA-treated patients had a high comorbidity profile and compared to the first-generation potassium binders, patients initiating second generation potassium binders had more comorbidities and longer K+ binder treatment duration. Overall, potassium binder users still dose reduced MRA to a large degree. Whether second generation binders lead to..."

Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Heart Failure • Hypertension • Metabolic Disorders • Nephrology

Effects of 3.0 mEq/L [K+] Dialysate with Sodium Zirconium Cyclosilicate (SZC) vs. 2.0 mEq/L [K+] Dialysate without SZC on Cardiac Arrhythmia Rates (KIDNEY WEEK 2024) - "Among patients receiving maintenance HD with a history of hyperkalemia, a combination of dK+ 3.0 mEq/L and SZC on non-HD days reduced the rates of AF, CSCA, and post-HD hypokalemia compared with dK+ 2.0 mEq/L and no SZC."

Late-breaking abstract • Atrial Fibrillation • Cardiovascular

Effects of Sodium Zirconium Cyclosilicate on Quality of Life in Patients Undergoing Hemodialysis with Hyperkalemia: Design and Rationale of the Y-QOL Study (KIDNEY WEEK 2024) - "The Y-QOL study aims to determine the effectiveness of SZC in improving QOL concerning dietary potassium intake restrictions in patients undergoing hemodialysis with hyperkalemia."

Clinical • HEOR • Chronic Kidney Disease • Nephrology • Renal Disease

Tacrolimus-Induced Type IV Renal Tubular Acidosis in an Orthotopic, Cadaveric Liver Transplant Patient (ACG 2024) - "With immediate treatment of intravenous dextrose 5% in water with sodium bicarbonate and sodium zirconium cyclosilicate, renal function, and electrolytes promptly recovered...There may be an increased risk of Type IV RTA in patients on tacrolimus who have a history of CKD or those who have developed CKD after transplantation, as seen in the case we present. As such, hepatologists must be aware of this possibility in tacrolimus treatment for deceased donor liver transplants, as failure to treat, could lead to fatal hyperkalemia, acidosis, increased complications, and mortality."

Clinical • Chronic Kidney Disease • Fibrosis • Gastrointestinal Cancer • Hepatitis C • Hepatocellular Cancer • Hepatology • Immunology • Infectious Disease • Metabolic Disorders • Nephrology • Oncology • Pediatrics • Renal Disease • Solid Organ Transplantation • Solid Tumor • Transplantation

Effects of dialysate potassium concentration of 3.0mEq/l with sodium zirconium cyclosilicate on dialysis-free days versus dialysate potassium concentration of 2.0mEq/l alone on rates of cardiac arrhythmias in hemodialysis patients with hyperkalemia. (PubMed, Kidney Int) - "Hypokalemia was less frequent (33 vs. 58 patients) with 3.0 potassium/SZC compared with 2.0 potassium/noSZC. Thus, in patients with hyperkalemia on maintenance hemodialysis, a combination of potassium 3.0 mEq/l and SZC on non-hemodialysis days reduced the rates of AF, other clinically significant arrhythmias, and post-dialysis hypokalemia compared with potassium 2.0/noSZC."

Journal • Atrial Fibrillation • Cardiovascular • Chronic Kidney Disease • Nephrology • Renal Disease • Ventricular Tachycardia

A Novel Potassium Binder Sodium Zirconium Cyclosilicate to Enable RAAS Inhibitor (RAASi) Use in the Treatment of Patients with Diabetic Kidney Disease: The Crystal Study (KIDNEY WEEK 2024) - "This study will provide the first evidence on how SZC optimizes RAASi treatment while controlling hyperkalemia in the Chinese population."

Clinical • Chronic Kidney Disease • Diabetic Nephropathy • Nephrology • Renal Disease

Avoiding Arrythmias by Personalizing Dialysate Concentration: A Case for Precision Medicine in Dialysis Patients. (PubMed, Kidney Int) - "In this issue of the journal, Charytan et al showed that, in HD patients with hyperkalemia (5.1 - 6.5 mEq/l), a dialysate concentration of 3 mEq/l combined with sodium zirconium cyclosilicate (SZC) on dialysis-free days is associated with a less rate of atrial fibrillation compared to a dialysate concentration of 2 mEq/l over 8 weeks. Despite the obvious limitations such as the small sample size, short treatment period and the absence of information on longer-term impact regarding patient important outcomes such as sudden death, this well-conceived pilot study provides impetus for larger prospective trials to test whether this personalized approach reduces major cardiovascular events and mortality."

Journal • Atrial Fibrillation • Cardiovascular

Evaluation of Monotherapy Sodium Zirconium Cyclosilicate Versus Sodium Polystyrene Sulfonate for Acute Hyperkalemia: A Cohort Study. (PubMed, Hosp Pharm) - "SZC monotherapy is at least as effective as SPS in treating mild hyperkalemia and may reduce serum potassium more quickly and to a greater degree than SPS. Future research in more severe hyperkalemia and with monitoring of potassium at regular intervals is needed to better understand the role and potential advantages of SZC over SPS."

Journal • Monotherapy

Sodium Zirconium Cyclosilicate for Renin-Angiotensin-Aldosterone System Inhibitor Optimization in Patients with Heart Failure with Reduced Ejection Fraction: A Retrospective Analysis. (PubMed, Cardiol Ther) - "Extended real-world treatment with the K+ binder SZC was effective at maintaining normokalemia, and was associated with a greater uptake of RAASi, a reduced rate of HHF, and improvements in cardiac biomarkers in patients with HFrEF."

Journal • Retrospective data • Cardiovascular • Congestive Heart Failure • Heart Failure

OPRA-HF: OPtimizing Aldosterone Receptor Antagonist Therapy by Sodium Zirconium Cyclosilicate in Heart Failure (clinicaltrials.gov) - P2 | N=110 | Recruiting | Sponsor: Michael Fu | N=230 ➔ 110 | Trial completion date: Dec 2024 ➔ Dec 2026 | Trial primary completion date: Dec 2024 ➔ Dec 2026

Enrollment change • Trial completion date • Trial primary completion date • Cardiovascular • Congestive Heart Failure • Heart Failure

Sodium Zirconium Cyclosilicate (SZC) to Enable Renin Angiotensin-Aldosterone System Inhibitor (RAASi) Use for Diabetic Kidney Disease: The CRYSTAL Study (KIDNEY WEEK 2024) - "This study showed that using SZC to manage hyperkalemia can help optimize RAASi treatment for Chinese stage 3–4 CKD patients with diabetes and hyperkalemia. This can facilitate the use of RAASi at higher, guideline-recommended doses to achieve its cardio-renal benefits for DKD pts experiencing hyperkalemia."

Late-breaking abstract • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Nephrology • Renal Disease

Updated Design and Status of CONTINUITY: A Phase 4 Study of Continued Postdischarge Sodium Zirconium Cyclosilicate in CKD (KIDNEY WEEK 2024) - P4 | "The CONTINUITY study (estimated completion: Dec 2024) will provide important evidence supporting either SoC or more active sK+ management with a K+ binder post discharge for pts with CKD admitted with HK. Protocol changes allow inclusion of a wider pt population and the potential to improve the clinical relevance of the results."

P4 data • Chronic Kidney Disease • Nephrology

Hyperkalemia-Related Health Care Resource Use (HRU) Associated with Short-Term vs. Long-Term Sodium Zirconium Cyclosilicate (SZC) Therapy in Patients with ESKD: The GALVANIZE Outcomes Study (KIDNEY WEEK 2024) - "Long-term SZC use among patients with ESKD was associated with significantly lower rates of HK-related HRU compared to short-term SZC use."

Clinical • Cardiovascular • Diabetes • Hypertension • Metabolic Disorders • Nephrology • Renal Disease

Real-World Utilization of Sodium Zirconium Cyclosilicate in Hyperkalemia Management in Italy (ISPOR-EU 2024) - "This study provides insights into the Italian real-world use of SZC. RAASi discontinuation and healthcare costs were lower with long-term SZC treatment."

Clinical • Real-world • Real-world evidence • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Diabetic Nephropathy • Heart Failure • Hypertension • Metabolic Disorders • Nephrology • Renal Disease

Unveiling the Dual Threat: Glofitamab-Induced AKI via Tumor Lysis and Cytokine Release Syndromes (KIDNEY WEEK 2024) - "Treated with 6 rounds of R-CHOP regimen, with some improvement 6 months ago. 6 weeks before admission, he developed spontaneous TLS, treated with rasburicase and IV fluids & was found to have metastatic recurrence of DLBCL. His tumor was treated with gemcitabine and oxaliplatin to no avail...Due to CRS risk, the patient received obinutuzumab pretreatment...Within 12 hours, he developed symptoms of CRS (fever, tachycardia, and hypotension) and was sent to ICU, received IV fluids, dexamethasone, and tocilizumab, which assisted with stabilizing his vitals...For TLS, he was treated with IV fluids, sodium zirconium cyclosilicate, and sevelamer...As both CRS and TLS can cause AKI, albeit through different mechanisms, nephrologists should closely monitor patients receiving glofitamab for both syndromes.. . ."

Cytokine release syndrome • Acute Kidney Injury • B Cell Lymphoma • Cardiovascular • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Hypotension • Lymphoma • Nephrology • Non-Hodgkin’s Lymphoma • Oncology • Renal Disease • CD20

KAYEXALATE INDUCED MASSIVE BOWEL NECROSIS: TIME TO RETIRE THIS DRUG? (CHEST 2024) - "Providers using sodium polystyrene sulfonate should be aware of this life-threatening complication, particularly in patients who have other risk factors. Sodium zirconium cyclosilicate, although expensive, is a safer alternative."

Acute Kidney Injury • CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Musculoskeletal Diseases • Nephrology • Orthopedics • Pain • Renal Disease • Septic Shock • Solid Organ Transplantation • Vascular Neurology

COVID-ASSOCIATED ORGANIZING PNEUMONIA WITH CLAD IN A LUNG TRANSPLANT PATIENT (CHEST 2024) - "He tested positive for COVID 19 a week prior and was given intravenous bamlanivimab the previous day...Hyperkalemia was treated with sodium zirconium cyclosilicate...He was able to be discharged with home oxygen after completing five days of dexamethasone & remdesivir. He was planned for another five days of remdesivir followed by resumption of prednisone... Patients with post COVID pneumonia must be evaluated for organizing pneumonia in order to initiate early treatment. In addition, lung transplant patients who develop COVID infection must be monitored for decline in their lung function."

Clinical • Anemia • Cardiovascular • Chronic Kidney Disease • Cough • Fatigue • Hematological Disorders • Infectious Disease • Nephrology • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • Thrombocytopenia • Transplantation