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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

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
  • Batlle, Daniel, Division of Nephrology and Hypertension, Department of Medicine, The Feinberg School of Medicine, Chicago, Illinois, United States
  • Kendrick, Jessica B., Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
  • Oluwatosin, Yemisi, Renal CVRM (US Medical), AstraZeneca, Wilmington, Delaware, United States
  • Kooienga, Laura, Colorado Kidney Care, Denver, Colorado, United States
  • Eudicone, James M., Renal CVRM (US Medical), AstraZeneca, Wilmington, Delaware, United States
  • Sundin, Anna-Karin, BioPharmaceuticals Medical (Evidence), AstraZeneca, Mölndal, Sweden
  • Guerrieri, Emily, Renal CVRM, AstraZeneca, Gaithersburg, Maryland, United States
  • Fried, Linda F., Division of Renal-Electrolyte, Veterans Affairs Pittsburgh Healthcare System and University of Pittsburgh, Pittsburgh, Pennsylvania, United States
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