Kidney Week

Abstract: TH-PO364

Impact of Sodium Zirconium Cyclosilicate on Serum Potassium and Bicarbonate in Patients with Hyperkalemia and Metabolic Acidosis Associated with CKD: NEUTRALIZE Study

Session Information

• Fluid, Electrolyte, Acid-Base Disorders: Clinical - I
  November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Fluid, Electrolytes, and Acid-Base Disorders

• 1102 Fluid, Electrolyte, and Acid-Base Disorders: Clinical

Authors

• Ash, Stephen R., Nephrology Department, Indiana University Health Arnett, Lafayette, Indiana, United States

Stephen R. Ash,

• Batlle, Daniel, Division of Nephrology and Hypertension, Department of Medicine, The Feinberg School of Medicine, Chicago, Illinois, United States

Daniel Batlle,

• Kendrick, Jessica B., Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

Jessica B. Kendrick,

• Oluwatosin, Yemisi, Renal CVRM (US Medical), AstraZeneca, Wilmington, Delaware, United States

Yemisi Oluwatosin,

• Kooienga, Laura, Colorado Kidney Care, Denver, Colorado, United States

Laura Kooienga,

• Eudicone, James M., Renal CVRM (US Medical), AstraZeneca, Wilmington, Delaware, United States

James M. Eudicone,

• Sundin, Anna-Karin, BioPharmaceuticals Medical (Evidence), AstraZeneca, Mölndal, Sweden

Anna-Karin Sundin,

• Guerrieri, Emily, Renal CVRM, AstraZeneca, Gaithersburg, Maryland, United States

Emily Guerrieri,

• Fried, Linda F., Division of Renal-Electrolyte, Veterans Affairs Pittsburgh Healthcare System and University of Pittsburgh, Pittsburgh, Pennsylvania, United States

Linda F. Fried,

Background

Acidosis and hyperkalemia are common in CKD. The dual effect of sodium zirconium cyclosilicate (SZC), a selective binder of potassium (K⁺) and ammonium, on serum K⁺ (sK⁺) and serum bicarbonate (sHCO3^-) was evaluated in CKD patients with hyperkalemia (HK) and metabolic acidosis.

Methods

In the NEUTRALIZE study (NCT04727528), patients with CKD (Stage 3–5) not on dialysis with HK (sK⁺ >5.1 to ≤5.9 mmol/L) and metabolic acidosis (sHCO3^- 16–20 mmol/L) received open-label SZC 10 g TID for ≤48 h. Patients achieving normokalemia (NK; sK⁺ 3.5–5.0 mmol/L) were randomized 1:1 to SZC 10 g QD or placebo (PBO) for 4 weeks. Primary endpoint was patients (%) maintaining NK at end of treatment (EOT) without rescue. Key secondary endpoints were patients (%) with NK with ≥3 mmol/L increase in sHCO3^- without rescue, and change in sHCO3⁻ from baseline (BL) to EOT.

Results

Patients (n=229) were screened and 37 were randomized and received treatment (SZC n=17; PBO n=20: high screen failure rate and slow enrolment led to early study termination). Mean age was 63.3y, 68% male, and 87% White. Mean sK⁺ (mmol/L) at BL was 5.4 (SZC) and 5.5 (PBO) and for sHCO3^- (mmol/L) 16.1 (SZC) and 15.6 (PBO). At EOT, patients maintaining NK was 88.2% for SZC and 20.0% for PBO (OR, SZC vs PBO, 56.2; P=0.001). Due to small patient number, P-values for secondary endpoints are nominal. sHCO3⁻ (mmol/L) at EOT was 18.2 for SZC vs 16.5 for PBO (P=0.050). Patients maintaining NK and ≥3 mmol/L increase in sHCO3^- without rescue was 35.3% (SZC) and 5.0% (PBO; P<0.05). For SZC, trends were seen towards a decrease in sK⁺ and an increase in sHCO3^- (Figure). No safety concerns were reported.

Conclusion

SZC effectively lowered sK⁺ and maintained NK during treatment. Despite low patient number, trends towards significance were seen for the increase in sHCO3^- with SZC.

Funding

• Commercial Support – AstraZeneca