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Kidney Week

Abstract: PO1414

Effect of Patiromer and Sodium Zirconium Cyclosilicate on Blood Pressure in a Rat CKD Model Induced by 5/6th Nephrectomy

Session Information

Category: Fluid, Electrolyte, and Acid-Base Disorders

  • 901 Fluid, Electrolyte, and Acid-Base Disorders: Basic

Authors

  • Li, Lingyun, Relypsa, Inc., a Vifor Pharma Group Company, Redwood City, California, United States
  • Conrad, Ansgar, Relypsa, Inc., a Vifor Pharma Group Company, Redwood City, California, United States
  • Romero, Alain, Relypsa, Inc., a Vifor Pharma Group Company, Redwood City, California, United States
  • Bushinsky, David A., University of Rochester School of Medicine, Rochester, New York, United States
Background

Patiromer (PAT) is a sodium-free, non-absorbed polymer drug approved for treatment of hyperkalemia (HK) in adults. In clinical studies of patients with CKD and HK, decreases in BP were observed during PAT treatment. The objective of this study was to evaluate effect of PAT and another K+ binder, sodium zirconium cyclosilicate (SZC), on BP in a CKD rat model.

Methods

36 Sprague Dawley (SD) rats underwent 5/6 nephrectomy (Nx) and each had a telemetry device implanted. Animals were randomized into 3 groups of 12. PAT (4 g/kg), SZC (4 g/kg), or vehicle was administered daily via oral gavage for 8 wks. Telemetry data was collected for at least 24 hrs once weekly from baseline (BL). Blood and urine samples were collected weekly. All values are mean ± SD.

Results

Systolic BP from BL to Wk 8 increased in vehicle-treated rats (136 ± 4.0 mmHg to 154 ± 4.8 mmHg), PAT-treated rats (132 ± 3.7 mmHg to 140 ± 3.6 mmHg), and SZC-treated rats (135 ± 4.1 mmHg to 158 ± 5.3 mmHg). PAT-treated rats had significantly lower systolic BP at Wk 8 compared to rats in vehicle and SZC-treated groups (P<0.001) (Figure). Mean BP change from BL in PAT-treated rats (8 ± 3.2 mmHg) was significantly lower vs vehicle group (18 ± 2.9 mmHg, P<0.001) and vs SZC-treated group (23 ± 4.2 mmHg, P<0.001), while mean BP change from BL in SZC-treated rats was significantly higher vs vehicle group (P<0.005). Serum K+ levels were in range of normokalemia (4.0-6.2 mEq/L in normal SD rats) from BL to Wk 8 in all groups (5.6 ± 0.26 mEq/L to 5.5 ± 0.22 mEq/L in vehicle-treated rats, 5.6 ± 0.43 mEq/L to 5.5 ± 0.25 mEq/L in PAT-treated rats, and 5.3 ± 0.36 mEq/L to 4.9 ± 0.35 mEq/L [P=0.02] in SZC-treated rats). There was no difference in serum creatinine levels among the 3 groups during the study.

Conclusion

With 8 wks of PAT treatment, SD rats with 5/6 Nx exhibited significantly lower BP compared to vehicle-treated and SZC-treated rats. Additional analyses are warranted to determine mechanism of PAT’s effect on BP in this model of CKD.

Funding

  • Commercial Support