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.

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Publisher Full Text

Authors

Schiavi SC, Tang W, Bracken C, O'Brien SP, Song W, Boulanger J, Ryan S, Phillips L, Liu S, Arbeeny C, Ledbetter S, Sabbagh Y

Institution

The Sanofi-Genzyme R&D Center, 49 New York Avenue, Framingham, MA 01701-9322, USA. susan.schiavi@genzyme.com

Source

Journal of the American Society of Nephrology : JASN 23:10 2012 Oct pg 1691-700

MeSH

Animals
Disease Models, Animal
Fibroblast Growth Factors
Humans
Hyperphosphatemia
Mice
Mice, Knockout
Polyamines
Renal Insufficiency, Chronic
Renal Osteodystrophy
Sodium-Phosphate Cotransporter Proteins, Type IIb
Uremia

Pub Type(s)

Journal Article

Language

eng

PubMed ID

22859851