title: Preclinical studies of VS-505: a non-absorbable highly effective phosphate binder.
abstract: Phosphate imbalance is often present in chronic kidney disease (CKD), and it contributes to a higher cardiovascular mortality rate. A phosphate binder is typically part of a treatment strategy for controlling phosphate imbalance. However, safety concerns and low compliance are two well-recognized disadvantages of on-market phosphate binders. This report describes the preclinical studies of VS-505, a non-absorbable, calcium- and aluminum-free, plant-derived polymer currently being evaluated in haemodialysis patients in Australia.
  
  
  
  Normal Sprague Dawley (SD) rats or uraemic SD rats induced by 5/6 nephrectomy fed a high-phosphate diet were treated with VS-505 or sevelamer (0.05-10% in food) for 5 and 28 days respectively.
  
  
  
  Urinary and serum phosphate levels were significantly elevated in untreated rats, and were decreased by VS-505 and sevelamer. VS-505 increased faecal phosphate levels in a dose-dependent manner. High-phosphate diet also caused an increase in serum FGF-23 and parathyroid hormone in nephrectomized (NX) rats, effects prevented by VS-505 or sevelamer. Significant aortic calcification was observed in NX rats treated with 5% sevelamer, whereas VS-505 at all doses tested did not show effects. VS-505 had no effects on small intestine histomorphology and intestinal sodium-dependent phosphate cotransporter gene expression. In vitro characterizations showed that VS-505 has a relatively high density and low expansion volume when exposed to simulated gastric fluid.
  
  
  
  VS-505 is a safe and effective phosphate binder and may offer the advantage of having a reduced pill burden and minimal GI side effects for CKD patients.
authors.affiliation: Vidasym, Chicago, IL, USA.
authors.forename: J Ruth
authors.initials: JR
authors.lastname: Wu-Wong
authors.affiliation: Vidasym, Chicago, IL, USA.
authors.forename: Yung-Wu
authors.initials: YW
authors.lastname: Chen
authors.affiliation: University of Iowa, Iowa City, IA, USA.
authors.forename: Jonathan T
authors.initials: JT
authors.lastname: Wong
authors.affiliation: Vidasym, Chicago, IL, USA.
authors.forename: Jerry L
authors.initials: JL
authors.lastname: Wessale
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D006170:Gum Arabic / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D010710:Phosphates / Q000097:blood / Q000737:chemistry / Q000378:metabolism* / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D010710:Phosphates; D006170:Gum Arabic