title: Npt2b deletion attenuates hyperphosphatemia associated with CKD.
abstract: The incidence of cardiovascular events and mortality strongly correlates with serum phosphate in individuals with CKD. The Npt2b transporter contributes to maintaining phosphate homeostasis in the setting of normal renal function, but its role in CKD-associated hyperphosphatemia is not well understood. Here, we used adenine to induce uremia in both Npt2b-deficient and wild-type mice. Compared with wild-type uremic mice, Npt2b-deficient uremic mice had significantly lower levels of serum phosphate and attenuation of FGF23. Treating Npt2b-deficient mice with the phosphate binder sevelamer carbonate further reduced serum phosphate levels. Uremic mice exhibited high turnover renal osteodystrophy; treatment with sevelamer significantly decreased the number of osteoclasts and the rate of mineral apposition in Npt2b-deficient mice, but sevelamer did not affect bone formation and rate of mineral apposition in wild-type mice. Taken together, these data suggest that targeting Npt2b in addition to using dietary phosphorus binders may be a therapeutic approach to modulate serum phosphate in CKD.
authors.affiliation: The Sanofi-Genzyme R&D Center, 49 New York Avenue, Framingham, MA 01701-9322, USA. susan.schiavi@genzyme.com
authors.forename: Susan C
authors.initials: SC
authors.lastname: Schiavi
authors.forename: Wen
authors.initials: W
authors.lastname: Tang
authors.forename: Christina
authors.initials: C
authors.lastname: Bracken
authors.forename: Stephen P
authors.initials: SP
authors.lastname: O'Brien
authors.forename: Wenping
authors.initials: W
authors.lastname: Song
authors.forename: Joseph
authors.initials: J
authors.lastname: Boulanger
authors.forename: Susan
authors.initials: S
authors.lastname: Ryan
authors.forename: Lucy
authors.initials: L
authors.lastname: Phillips
authors.forename: Shiguang
authors.initials: S
authors.lastname: Liu
authors.forename: Cynthia
authors.initials: C
authors.lastname: Arbeeny
authors.forename: Steven
authors.initials: S
authors.lastname: Ledbetter
authors.forename: Yves
authors.initials: Y
authors.lastname: Sabbagh
mesh_terms: D000818:Animals; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D004195:Disease Models, Animal; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism; D006801:Humans; D054559:Hyperphosphatemia / Q000209:etiology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011073:Polyamines / Q000494:pharmacology; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D000069603:Sevelamer; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb / Q000172:deficiency* / Q000235:genetics; D014511:Uremia / Q000150:complications / Q000378:metabolism
chemical_list: C000717427:FGF23 protein, human; C000717428:Fgf23 protein, mouse; D011073:Polyamines; C493558:Slc34a2 protein, mouse; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D000069603:Sevelamer