Lokelma (sodium zirconium cyclosilicate) / AstraZeneca - LARVOL DELTA

Impact of a plant-based food basket on uremic toxins, dietary patterns and carbon footprint in patients with chronic kidney disease (ERA 2025) - P=N/A | "This is a sub-analysis of a feasibility clinical trial conducted in patients with CKD and hyperkalemia at inclusion who received sodium zirconium cyclosilicate (SZC) to achieve acceptable plasma potassium levels... The implementation of a plant-based food basket in patients with CKD led to a significant reduction in UPF intake, highlighting the potential for dietary interventions to encourage healthier food choices. However, no significant changes were observed in GHGEs, uremic toxins' and UPF metabolomic markers' levels. As this is a feasibility trial, the findings suggest dietary modifications improved quality, but larger samples and additional strategies may be needed to reduce GHGEs and uremic toxins."

Clinical • Chronic Kidney Disease • Nephrology • Renal Disease

Epidemiological Profile of Patients with Diabetic Kidney Disease and Heart Failure Initiating Finerenone: Insights from Real-World Data. (ERA 2025) - "Of these, 20.9% were MRA-naïve patients, while 79.1% were previously on an MRA; 38.7% were on spironolactone, and 40.4% were on eplerenone...Diuretics were used by 74.2%, predominantly furosemide (95.7%), with a mean dose of 30 mg, predominantly furosemide (95.7%), with a mean dose of 30 mg...Potassium binders were used by 29,1% of patients (12.9% calcium polystyrene sulfonate and 16,2% sodium zirconium cyclosilicate)... These findings provide a comprehensive profile of patients with HF and DKD initiating finerenone in a real-world cohort, highlighting the significant burden of comorbidities and the interplay between cardiac and renal dysfunction in this population. The clinical, laboratory, and treatment parameters data underscores the complexity of managing these high-risk patients in real-world settings. A longer follow-up is needed to know the finerenone impact in this population."

Clinical • Real-world • Real-world evidence • Cardiomyopathy • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Coronary Artery Disease • Diabetes • Diabetic Nephropathy • Dyslipidemia • Heart Failure • Hypertension • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

Serum potassium and dialysate potassium prescription in a maintenance in- centre haemodialysis cohort (UKKW 2025) - "Data from three consecutive monthly pre-dialysis sessions including serum potassium, dietetic input, dialysate prescription and use of an oral potassium binder (Lokelma) was collected between September and December 2024 via the renal dietitians' datasheet and our local renal electronic health record (VitalData)...Overall, our results point to a need for more focus on hypokalaemic patients for dietetic support and judicious high-potassium dialysate prescription on the monthly multi-disciplinary team review. We plan to undertake a quality improvement project to raise the salience of dialysate potassium prescription in our unit and to focus as much on patients with hypokalaemia."

Clinical • Cardiovascular • Renal Disease

How hyperkalaemia limits optimisation of treatment in a community chronic kidney disease (CKD) setting (UKKW 2025) - "54 patients (13%) had potassium levels above 5.1mmol/l. Of these, 28 (52%) were referred to a dietitian, and 27 (50%) of these attended an appointment. All patients with a potassium >6mmol/l received dietetic intervention."

Cardiovascular • Chronic Kidney Disease • Diabetes • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

Outcomes and Resource Utilization in Hyperkalemic Emergency Department Patients Treated With Patiromer or Sodium Zirconium Cyclosilicate. (PubMed, J Am Coll Emerg Physicians Open) - "Patients receiving patiromer had lower in-hospital mortality. Patients receiving SZC had lower 30-day all-cause and hyperkalemia-related hospitalization risks."

HEOR • Journal

The ORTIZ Study: Optimising RASi Therapy With SZC (clinicaltrials.gov) - P2 | N=18 | Terminated | Sponsor: Barts & The London NHS Trust | N=10 ➔ 18

Enrollment change • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

VITALIZE.Use and Effectiveness of Sodium Zirconium Cyclosilicate (LokelmaTM) in the Real-world Setting in Spain (clinicaltrials.gov) - P=N/A | N=232 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

Real-world evidence • Trial completion

Hypertension and hyperkalemia associated with Pro701Leu mutation in the NR3C2 gene: A case report. (PubMed, Medicine (Baltimore)) - "This case highlights the importance of genetic testing in diagnosing complex cases of hypertension and hyperkalemia. The discovery of the Pro701Leu mutation in the NR3C2 gene underscores the need for further research into its pathophysiological mechanisms and therapeutic implications. Early recognition and tailored treatment can improve patient outcomes in similar cases."

Journal • Bipolar Disorder • Cardiovascular • Chronic Obstructive Pulmonary Disease • CNS Disorders • Heart Failure • Hepatitis C • Hypertension • Immunology • Infectious Disease • Inflammation • Mood Disorders • Psychiatry • Pulmonary Disease • Respiratory Diseases

Guideline-Recommended Disease-Modifying Therapies for Patients with Cardiorenal Disease: A Call-to-Action Narrative Review. (PubMed, Adv Ther) - "Hyperkalemia can be managed and optimal RASi dosing can be continued by using novel potassium binders, such as sodium zirconium cyclosilicate or patiromer. In doing so, the guideline targets achievement of the "quadruple aim" of GDMT in CKD, i.e., enabling optimal use of RASi and SGLT2i in most patients, along with nonsteroidal mineralocorticoid receptor antagonists, and glucagon-like peptide-1 receptor agonists in diabetic kidney disease. This manuscript constitutes a call to action to raise awareness of the growing clinical and economic burdens of CKD and to promote a united approach to the early detection and optimal treatment of CKD through stricter adherence to GDMT."

Journal • Review • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Gastrointestinal Disorder • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

Intermittent sodium zirconium cyclosilicate for the prevention of hyperkalemia in chronic kidney disease. (PubMed, BMC Nephrol) - "Intermittent SZC treatment may help prevent hyperkalemia in CKD patients. Further research is necessary to ascertain if this benefit translates into improvements in hard clinical outcomes."

Journal • Chronic Kidney Disease • Nephrology • Renal Disease

Practice Patterns of Potassium-binding Agent Use for Severe Acute Hyperkalemia in Intensive Care Units (ATS 2025) - " Using PINC AI Healthcase Database, we identified adults (age ≥18) with severe hyperkalemia (serum potassium ≥6.0 mmol/L) admitted to ICUs May 2018 - September 2022 and received any of three potassium-binding agents: Sodium polystyrene sulfate (SPS; Kayexalate®), sodium zirconium cyclosilicate (SZC; Lokelma®), or patiromer. Few ICU patients with severe acute hyperkalemia received a potassium-binding agent on presentation, but if used, there was significant variation between hospitals in the choice of agent. We theorize this may be partly explained by the high cost of new potassium-binding agents relative to SPS. Notably, the use of new potassium-binding agents increased although no comparative effectiveness clinical trials have been completed to date."

Cardiovascular • Critical care • Nephrology • Renal Disease

Spontaneous Tumor Lysis Syndrome in a Patient With Serous Endometrial Carcinoma (ATS 2025) - "She received calcium gluconate, dextrose with insulin, sodium-zirconium cyclosilicate, and albuterol, resulting in a potassium decrease to 6.5 mmol/L...Despite midodrine, she remained dependent on vasopressors...TLS mortality ranges from 27-79% depending on the underlying malignancy, making early recognition and treatment with Rasburicase critical in preventing acute and long-term complications. In the absence of prior cytotoxic therapy, clinicians are less likely to suspect TLS and treatment may be delayed. This case underscores the need for heightened vigilance in critical care for spontaneous TLS, especially in gynecologic malignancies, where rapid progression to multi-organ failure demands prompt management to mitigate life-threatening complications."

Clinical • Cardiovascular • CNS Disorders • Endometrial Cancer • Epilepsy • Heart Failure • Hematological Malignancies • Hypotension • Metabolic Disorders • Nephrology • Oncology • Renal Disease • Solid Tumor

Sodium zirconium cyclosilicate for the management of hyperkalaemia in patients with heart failure with reduced ejection fraction - the REALIZE-K open-label run-in phase (HEART FAILURE 2025) - "Background: The REALIZE-K trial, which enrolled participants (pts) with heart failure and reduced ejection fraction (HFrEF) and hyperkalaemia (HK), showed that the novel potassium (K+) binder sodium zirconium cyclosilicate (SZC) led to large increases in the percentage of pts with normokalaemia while on optimal doses of spironolactone (SPL), and reduced HK risk and down-titration/discontinuation of SPL... In cohort 1 (pts with prevalent HK on no, or low dose, SPL/eplerenone) there was a 4-wk OL run-in period... Of 95 and 271 pts enrolled in cohort 1 and 2, respectively, 94 and 147 received ≥1 dose of SZC. Cohort 1 mean age was 70.5 yrs, 31.6% had type 2 diabetes (T2D), and mean estimated glomerular filtration rate (eGFR) was 56.4 mL/min/1.73 m2. SZC resulted in HK resolution within 48 h in 79.8% of pts."

Clinical • Cardiovascular • Congestive Heart Failure • Heart Failure

Epidemiological profile of heart failure patients with diabetic kidney disease initiating finerenone: insights from real-world data (FINARM STUDY) (HEART FAILURE 2025) - "Diuretics were used by 74.2%, predominantly furosemide (95.7%), with a mean dose of 30 mg...Potassium binders were used by 29.1% (12.9% calcium polystyrene sulfonate and 16.2% sodium zirconium cyclosilicate)... These findings provide a comprehensive profile of patients with HF and DKD initiating finerenone in a real-world cohort, highlighting the burden of comorbidities and the interplay between cardiac and renal dysfunction in this population. The collected data underscores the complexity of managing these high-risk patients. A longer follow-up is needed to know the finerenone impact in this population."

Clinical • Real-world • Real-world evidence • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Coronary Artery Disease • Dyslipidemia • Heart Failure • Hypertension

Sodium zirconium cyclosilicate versus sodium polystyrene sulfonate for treatment of hyperkalemia in hemodialysis patients: a randomized clinical trial. (PubMed, BMC Nephrol) - P=N/A | "When compared to SPS treatment, SZC was associated with a more rapid and efficacious resolution of hyperkalemia with potentially a better safety profile and palatability among HD patients."

Clinical • Journal • Gastrointestinal Disorder • Renal Disease

Prognostic Impact of Long-Term Sodium Zirconium Cyclosilicate-Integrated Medical Therapy in Patients with Systolic Heart Failure. (PubMed, J Clin Med) - " Long-term SZC-integrated medical therapy was associated with the sustained normalization of hyperkalemia, optimization of heart failure pharmacotherapy, and improved clinical outcomes in patients with systolic heart failure and baseline hyperkalemia. These findings underscore the need for prospective randomized controlled trials in carefully selected patient populations to validate the benefits of SZC and establish its optimal supportive role in the management of systolic heart failure."

Journal • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Heart Failure • Nephrology • Renal Disease

Sodium Zirconium Cyclosilicate for the Acute Management of Hyperkalemia in the Emergency Department. (PubMed, Ann Pharmacother) - "The optimal use of SZC in the acute management remains uncertain based on results from this study with no difference in potassium levels at first recheck."

Journal

Efficacy and safety of calcium polystyrene sulphonate and sodium zirconium cyclosilicate as potassium binders for chronic hyperkalemia in hemodialysis patients: A prospective study. (PubMed, Clin Nephrol) - "SZC demonstrated superior effectiveness in reducing potassium levels and controlling severe hyperkalemia in patients undergoing maintenance HD. It also facilitated more rapid control of serum potassium levels offering an improved long-term management strategy for chronic hyperkalemia."

Clinical • Journal • Chronic Kidney Disease • Nephrology • Renal Disease

The role of sodium zirconium cyclosilicate drug utilization in managing hyperkalemia: impact on healthcare resource utilization and on maintenance of renin-angiotensin-aldosterone system inhibitor therapy in Italian clinical practice. (PubMed, J Med Econ) - "This real-world study showed that nearly 17% of patients continued SZC therapy for ≥90 days. Long-term therapy was associated with lower RAASi discontinuation and reduced healthcare costs due to hospitalizations and outpatient specialist services, suggesting that SZC can potentially provide clinical and economic benefits for HK management."

HEOR • Journal • Retrospective data • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Heart Failure • Hypertension • Metabolic Disorders • Nephrology • Renal Disease

VITALIZE.Use and Effectiveness of Sodium Zirconium Cyclosilicate (LokelmaTM) in the Real-world Setting in Spain (clinicaltrials.gov) - P=N/A | N=233 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Real-world evidence

OPRA-HF: OPtimizing Aldosterone Receptor Antagonist Therapy by Sodium Zirconium Cyclosilicate in Heart Failure (clinicaltrials.gov) - P2 | N=110 | Active, not recruiting | Sponsor: Michael Fu | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2026 ➔ Jun 2026 | Trial primary completion date: Dec 2026 ➔ Dec 2025

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

THE JOURNEY OF BRASH AS NARRATED BY A PACEMAKER - Prutha R. Pathak (ACC 2025) - "Background: Bradycardia, renal insufficiency, AV nodal block, shock, and hyperkalemia (BRASH) causing pacemaker capture failure, i.e., the inability of a pacing impulse to produce an evoked potential, has rarely been described.Case: A 66-year-old woman with atrial fibrillation and sick sinus syndrome s/p dual-chamber pacemaker a month ago (on metoprolol succinate) and heart failure with preserved ejection fraction (on spironolactone, furosemide, and potassium chloride) presented with generalized weakness for 24 hours...Investigations demonstrated potassium of 9.4 mEq/dl, AKI (creatinine of 1 mg/dL from 0.6 at baseline), and capture failure on EKG.Decision-making: The patient was diagnosed with BRASH and resuscitated with intravenous fluids, norepinephrine, calcium gluconate, insulin, and sodium zirconium cyclosilicate. Recognizing BRASH as an important reversible cause of pacemaker capture failure and its immediate management is crucial in preventing cardiovascular..."

Atrial Fibrillation • Cardiovascular • Congestive Heart Failure • Dermatology • Heart Failure • Hypotension • Nephrology • Renal Disease

Updates in chronic kidney disease management: A systematic review. (PubMed, Pharmacotherapy) - "Currently, SGLT2i have demonstrated consistent benefits with large effect sizes in preventing the progression of CKD, solidifying this class as a first-line treatment along with RASi. Subsequent consideration for GLP-1RA, finerenone, and sacubitril/valsartan should be dependent on patient-specific comorbidities, while potassium binders may allow for longer use of RASi."

Journal • Review • Chronic Kidney Disease • Nephrology • Renal Disease

Post-marketing safety associated with sodium zirconium cyclosilicate: a pharmacovigilance study based on the FDA reporting system. (PubMed, Expert Opin Drug Saf) - "Furthermore, AEs differed between male and female patients. This study confirmed SZC label safety warnings and identified new AEs, offering insights for clinical monitoring of SZC."

Adverse events • Journal • P4 data • Cardiovascular • Congestive Heart Failure • Constipation • Gastroenterology • Gastrointestinal Disorder • Heart Failure • Infectious Disease • Pneumonia • Respiratory Diseases

Safety assessment of sodium zirconium cyclosilicate: A FAERS-based disproportionality analysis. (PubMed, PLoS One) - "This study confirms common AEs of SZC and identifies new ones, highlighting the need for careful monitoring and facilitating its safe use in clinical settings. However, disproportionality analysis cannot formally prove causation and further studies are needed to confirm these associations."

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