Lokelma (sodium zirconium cyclosilicate) / AstraZeneca - LARVOL DELTA

Management of patients with heart failure at high risk of hyperkalaemia: The CARE-HK in HF registry. (PubMed, Eur J Heart Fail) - P | "In this contemporary multinational prospective registry of patients with HF at high risk for hyperkalaemia, hyperkalaemic events were common but infrequently associated with RASi/MRA modification or potassium binder use. Fewer than one in three patients received optimal RASi/MRA therapy for the majority of follow-up, and hyperkalaemic events were associated with higher risk of adverse clinical outcomes."

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

SENEKA: A Clinical Trial to Define the Best Strategy for the Management of Heart Failure in Elderly Patients (clinicaltrials.gov) - P3 | N=94 | Recruiting | Sponsor: Fundación para la Investigación del Hospital Clínico de Valencia | Trial completion date: Mar 2026 ➔ Dec 2026 | Trial primary completion date: Mar 2025 ➔ Dec 2025

Trial completion date • Trial primary completion date • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Heart Failure • Nephrology • Renal Disease

KBindER: Comparison of Potassium Binders in the ER (clinicaltrials.gov) - P4 | N=37 | Terminated | Sponsor: University of California, Irvine | N=120 ➔ 37 | Trial completion date: Dec 2025 ➔ Jan 2025 | Recruiting ➔ Terminated | Trial primary completion date: Jul 2025 ➔ Jan 2025; Low enrollment rate

Enrollment change • Trial completion date • Trial primary completion date • Trial termination

Sodium zirconium cyclosilicate (Lokelma) to enable ACEIs/ARBs use in the treatment of patients with diabetic kidney disease. (PubMed, Diabetes Res Clin Pract) - "SZC reduced hyperkalemia-related RAASi discontinuation risk, improved proteinuria and BP, supporting its prophylactic use in DKD patients on RAASi."

Clinical • Journal • Diabetic Nephropathy • Nephrology • Renal Disease

Cardiovascular disease treatment and hyperkalemia: A report of three cases. (PubMed, Med Int (Lond)) - "Acute hyperkalemia developed due to angiotensin converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB) and spironolactone in 3 patients, whose cases are reported herein. Sodium zirconium cyclosilicate may be the preferred treatment in emergency cases of hyperkalemia due to its rapid effects. On the other hand, sodium glucose co-transporter 2 inhibitors and non-steroidal mineralocorticoid receptor antagonists may also be used to avoid the development of hyperkalemia in patients undergoing RAASi therapy."

Journal • Acute Kidney Injury • Cardiovascular • Hypertension • Nephrology • Renal Disease

Comparison of Three Potassium Binders in Patients With Acute Hyperkalemia. (PubMed, Cureus) - "SPS and SZC were superior to patiromer in lowering serum potassium levels in patients with acute hyperkalemia, with no significant difference between SPS and SZC. Considering the established safety concerns associated with SPS, SZC may be the preferred binder for managing acute hyperkalemia in the inpatient setting."

Journal • Cardiovascular • Chronic Kidney Disease • Nephrology • Renal Disease

Sodium Zirconium Cyclosilicate in the Gastrointestinal Tract Mimicking an Acute Gastrointestinal Bleed on CT. (PubMed, Reports (MDPI)) - "Further investigation of the patient's medical record showed that the patient was being treated with SZC for hyperkalemia, accounting for the hyperattenuating cecal contents. Awareness of the hyperattenuating appearance of SZC on CT by radiologists and clinical staff can help avoid confusion and misdiagnosis."

Journal • Gastrointestinal Disorder

Novel Drugs and Hyperkalemia: Risks and Solutions: Electrolyte Disorders in CKD and the Elderly: Clinical Challenges and Emerging Solutions (KSN 2025) - "Recently, finerenone, a non-steroidal mineralocorticoid receptor antagonist has become available to treat patients with type 2 diabetes...Sacubitril/valsartan, a new pharmacological class of angiotensin receptor neprilysin inhibitor, is beneficial to heart failure through blocking the degradation of natriuretic peptides and inhibiting renin-angiotensin-aldosterone system (RAAS) activation which also relate to the pathophysiologic mechanisms of chronic kidney disease...Patiromer and sodium zirconium cyclosilicate (SZC) are newer options for hyperkalemia treatment...Recent randomized clinical trials have shown that SZC effectively lowers serum potassium and maintains normokalemia in most hyperkalemic patients. It is likely these newer oral potassium-binding agents will help change how patients with hyperkalemia are treated in regards to sudden and chronic medical conditions."

Clinical • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Heart Failure • Metabolic Disorders • Nephrology • Type 2 Diabetes Mellitus

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 | Trial completion date: Jun 2026 ➔ Dec 2025

Trial completion date • Cardiovascular • Congestive Heart Failure • Heart Failure

The randomized DIALIZE-Outcomes trial evaluated sodium zirconium cyclosilicate in hemodialysis. (PubMed, Kidney Int) - "SZC did not demonstrate a treatment effect on arrhythmia-related cardiovascular outcomes despite efficacy on serum potassium control."

Journal • Cardiovascular • Chronic Kidney Disease • Nephrology • Renal Disease

Hyperkalemia in Hemodialysis: Use of Sodium Zirconium Cyclosilicate - A Single-center Experience (PubMed, G Ital Nefrol) - "Recently, two new medications have been introduced for chronic potassium control: Patiromer and Sodium Zirconium Cyclosilicate, the latter approved for use in haemodialysis. We conducted an observational study at our dialysis unit on 28 chronic haemodialysis patients, where after detecting hyperkalaemia, therapy with Sodium Zirconium Cyclosilicate was initiated. We evaluated the potassium levels over time, changes in home treatments, and the drug's tolerability."

Journal • Observational data • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Heart Failure • Metabolic Disorders • Nephrology • Renal Disease

Correction: Sodium zirconium cyclosilicate versus sodium polystyrene sulfonate for treatment of hyperkalemia in hemodialysis patients: a randomized clinical trial. (PubMed, BMC Nephrol) - No abstract available

Clinical • Renal Disease

Renin-Angiotensin-Aldosterone System Inhibitor Dosing After Initiation of Outpatient Sodium Zirconium Cyclosilicate Therapy: The GALVANIZE RAASi Real-World Evidence Study. (PubMed, Adv Ther) - "In this real-world study of patients with RAASi use after SZC initiation, about two-thirds of patients had an optimized RAASi dose and more than a quarter of patients had a maximized RAASi dose within 6 months of starting SZC. Findings were consistent across sub-studies of patients with CKD, HF and treatment with MRA. SZC may support the maintenance of optimal RAASi therapy; however, further comparative analyses are warranted. Graphical abstract available for this article."

HEOR • Journal • Real-world evidence • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Heart Failure • Nephrology • Renal Disease

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