Npt2b Deletion Attenuates Hyperphosphatemia Associated with CKD

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 understo...

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Bibliographic Details
Published in:Journal of the American Society of Nephrology 2012-10, Vol.23 (10), p.1691-1700
Main Authors: SCHIAVI, Susan C, WEN TANG, LEDBETTER, Steven, SABBAGH, Yves, BRACKEN, Christina, O'BRIEN, Stephen P, WENPING SONG, BOULANGER, Joseph, RYAN, Susan, PHILLIPS, Lucy, SHIGUANG LIU, ARBEENY, Cynthia
Format: Article
Language:English
Subjects:
Animals
Basic Research
Biological and medical sciences
Chronic Kidney Disease-Mineral and Bone Disorder - drug therapy
Chronic Kidney Disease-Mineral and Bone Disorder - etiology
Chronic Kidney Disease-Mineral and Bone Disorder - metabolism
Disease Models, Animal
Fibroblast Growth Factors - metabolism
Humans
Hyperphosphatemia - etiology
Hyperphosphatemia - metabolism
Kidneys
Medical sciences
Mice
Mice, Knockout
Nephrology. Urinary tract diseases
Nephropathies. Renovascular diseases. Renal failure
Polyamines - pharmacology
Renal failure
Renal Insufficiency, Chronic - complications
Renal Insufficiency, Chronic - drug therapy
Renal Insufficiency, Chronic - metabolism
Sevelamer
Sodium-Phosphate Cotransporter Proteins, Type IIb - deficiency
Sodium-Phosphate Cotransporter Proteins, Type IIb - genetics
Uremia - complications
Uremia - metabolism
Urinary system involvement in other diseases. Miscellaneous
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Summary: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.
ISSN:1046-6673
1533-3450
DOI:10.1681/ASN.2011121213