Kidney Week

Abstract: SA-OR107

Sucroferric Oxyhydroxide (PA21) Improves Mineral Homeostasis, Reduces Vascular Calcification, and Exerts a Beneficial Effect on Renal Function in a Rat Model with CKD

Session Information

• Vascular Calcification, FGF-23, and Phosphate
  October 27, 2018 | Location: 33C, San Diego Convention Center
  Abstract Time: 06:18 PM - 06:30 PM

Category: Bone and Mineral Metabolism

• 401 Bone and Mineral Metabolism: Basic

Authors

• Verhulst, Anja, University of Antwerp, Wilryk, ANTWERP, Belgium

Anja Verhulst, PhD

• Neven, Ellen, University of Antwerp, Wilryk, ANTWERP, Belgium

Ellen Neven,

• Walpen, Sebastian, Vifor Fresenius Medical Care Renal Pharma, Glattbrugg, Switzerland

Sebastian Walpen,

• Opdebeeck, Britt, University Antwerp, Edegem, Belgium

Britt Opdebeeck,

• Funk, Felix W., Vifor Pharma Management Ltd., Glattbrugg, Switzerland

Felix W. Funk,

• D'Haese, Patrick C., University Antwerp, Edegem, Belgium

Patrick C. D'Haese,

Background

PA21 (or sucroferric oxyhydroxide) is an efficacious, well-tolerated iron-based phosphate binder and a promising alternative to existing compounds. We aimed to evaluate the effect of PA21 on renal function, mineral homeostasis and vascular calcification in a CKD rat model.

Methods

To induce stable CKD, 64 male Wistar rats were administered a 0.25% adenine diet during for 8 weeks. CKD rats were assigned to 4 treatment groups: (i) vehicle (n=16), (ii) 2.5 g/kg/day PA21 (n=16), (iii) 5.0 g/kg/day PA21 (n=16) and (iv) 3.0 g/kg/day CaCO₃ (n=16). Evolution in renal function and mineral metabolism was followed by measurement of serum creatinine, phosphorus, calcium, 1,25 (OH)₂ vitamin D, PTH and FGF-23. Serum ionized calcium, iron, hematocrit, hemoglobin, pH and bicarbonate were also measured. Calcification was assessed by determining the calcium content in the arteries.

Results

Vehicle treated CKD rats developed severe renal impairment, with creatinine values around 3.5-4 mg/dL, and anemia as indicated by decreased serum hematocrit and hemoglobin levels. CKD went along with hyperphosphatemia, hypocalcemia, low 1,25 (OH)₂ vitamin D and high PTH and FGF-23 levels. Both PA21 and CaCO₃ treatment showed efficient phosphate binding capacity and prevented the pronounced increase in serum PTH. CKD rats treated with 2.5 or 5 g/kg PA21 showed significant lower serum creatinine and phosphorus levels and higher ionized calcium levels after 8 weeks of daily treatment as compared to vehicle treated CKD rats. The better preserved renal function with PA21 treatment went along with less severe anemia. Both PA21 doses prevented the dramatic increase in FGF-23, whereas CaCO₃ did not. Daily treatment with PA21 did not increase circulating iron levels. Finally, PA21 treatment significantly reduced the calcium content in the aorta as well as the carotid and femoral arteries, whereas CaCO₃ did not affect calcification in the arteries.

Conclusion

In contrast to CaCO₃, treatment with PA21 had, aside from its phosphate lowering capacity, a beneficial impact on the development towards severe CKD and prevented the pronounced rise in serum FGF-23. Arterial calcification was significantly reduced by PA21 treatment.

Funding

• Commercial Support – Vifor (International) Ltd.