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Curr Opin Nephrol Hypertens. 2005 Jul;14(4):318-24.

Recent findings in phosphate homeostasis.

Author information

1
Inserm U 426 et Institut Fédératif de Recherche 02, Faculty of Medicine, Xavier Bichat, Paris, France. prie@necker.fr

Abstract

PURPOSE OF REVIEW:

We summarize the most recent findings on the proteins that interact with sodium/inorganic phosphate (Na/Pi) cotransporters, the factors that regulate Pi homeostasis and their role in pathology.

RECENT FINDINGS:

Studies in animal models and cell lines identified proteins mandatory to correct trafficking of the kidney-specific Na/Pi cotransporter NPT2a and its control by the parathyroid hormone. Expression of the intestinal cotransporter NPT2b is controlled by calcitriol, the ubiquitin ligase Nedd-4 and the serum glucocorticoid inducible kinase. Recent data confirm that fibroblast growth factor 23 plays a central role in the control of Pi homeostasis. Mice disrupted for or overexpressing this gene exhibit significant alteration of Pi transport and calcitriol metabolism. In humans, fibroblast growth factor 23 mutations are responsible for autosomal hypophosphataemic rickets or tumoral calcinosis. This gene also seems to be involved in hyperparathyroidism in patients with chronic kidney disease. Several new phosphaturic factors have been identified. Moderate increases in serum Pi concentration may have deleterious effects on lifespan in humans with chronic kidney disease. Disruption of the Klotho gene in mice is associated with hyperphosphataemia and decreased lifespan. Polymorphisms in this gene, in humans and in mice, influence vascular calcification and survival.

SUMMARY:

Pi homeostasis depends on the activity of Na/Pi cotransporters in intestine and kidney. Na/Pi transporter activity is regulated by cellular and endocrine factors, among which fibroblast growth factor 23 plays a central role. Adequate control of Pi homeostasis is crucial, as a moderate increase in serum Pi concentration and polymorphisms in genes involved in Pi metabolism may influence the aging process and lifespan.

PMID:
15930998
[Indexed for MEDLINE]

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