Abstract: SA-PO898

VS-605, a Mg+2-gum Arabic complex, Is a Non-Absorbed, Calcium- and Aluminum-Free, Highly Effective Phosphate Binder

Session Information

  • Mineral Disease: CKD-Bone
    November 04, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Mineral Disease

  • 1203 Mineral Disease: CKD-Bone

Authors

  • Wu-Wong, J. Ruth, Vidasym, Chicago, Illinois, United States
  • Chen, Yung-wu, Vidasym, Chicago, Illinois, United States
  • Wessale, Jerry, Vidasym, Chicago, Illinois, United States
Background

Inadequate control of serum phosphate (Pi) in chronic kidney disease can lead to pathologies of clinical importance. Effectiveness of on-market phosphate binders is limited by safety concerns and low compliance due to large pill size/burden and gastrointestinal (GI) discomfort.

Methods

VS-605, a novel phosphate binder, is a polymer consisting of only Mg+2 and gum Arabic (a fiber component commonly used in food), with ~30% Mg+2 tightly complexed to gum Arabic (by X-ray photoelectron spectroscopy). VS-605 was evaluated for its efficacy and potential side effects in various pre-clinical studies including dosing 5/6 nephrectomized (NX) uremic SD rats with either VS-605 or sevelamer for 1 month.

Results

VS-605 has a high density at 1.89 g/cm3 (vs. 1.27 g/cm3 for sevelamer) as determined by helium pycnometer. When exposed to simulated gastric fluid, VS-605 exhibited a low swell volume at 0.3 cm3/ml/0.1 g (vs. 4 cm3/ml/0.1 g for sevelamer). After incubating with a phosphate buffer or in simulated gastric fluid for 24 hr at 37°C, VS-605 released <2% of Mg+2 into solution. In 5/6 NX uremic SD rats fed a high-phosphate diet, increasing dietary Pi led to an increase in serum Pi, which was prevented in rats treated with VS-605 or sevelamer (0.2 - 5% in food). Urinary Pi increased from 71 ± 19 at Week 0 to 785 ± 58 µmol/24 hr at Week 4 (p<0.001) in the vehicle-treated group; treatment with VS-605 or sevelamer (0.2 - 5% in food) reduced urinary phosphate in a dose-dependent manner (to 100 ± 28 and 102 ± 42 µmol/24 hr for 3% VS-605 and 5% sevelamer at Week 4, respectively). Concurrently, VS-605 or sevelamer increased fecal Pi in a dose-dependent manner. The high Pi diet also increased serum FGF-23 and parathyroid hormone in 5/6 NX rats, which was prevented by VS-605 or sevelamer. More aortic calcification was observed in the 5/6 NX rats treated with 5% sevelamer; neither VS-605 nor sevelamer exhibited any significant effects on intestine histology and intestinal sodium-dependent phosphate cotransporter gene expression.

Conclusion

These results support the conclusion that VS-605 effectively controls Pi imbalance in uremic rats by adsorbing dietary Pi in the GI tract. The minimal swell volume and high density of VS-605 may result in a potential advantage for a small pill size and reduced GI discomfort.