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Previous Volume 359:1128-1135 September 11, 2008 Number 11 Next

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SUMMARY

Impaired renal phosphate reabsorption, as measured by dividing the tubular maximal reabsorption of phosphate by the glomerular filtration rate (TmP/GFR), increases the risks of nephrolithiasis and bone demineralization. Data from animal models suggest that sodium–hydrogen exchanger regulatory factor 1 (NHERF1) controls renal phosphate transport. We sequenced the NHERF1 gene in 158 patients, 94 of whom had either nephrolithiasis or bone demineralization. We identified three distinct mutations in seven patients with a low TmP/GFR value. No patients with normal TmP/GFR values had mutations. The mutants expressed in cultured renal cells increased the generation of cyclic AMP (cAMP) by parathyroid hormone (PTH) and inhibited phosphate transport. These NHERF1 mutations suggest a previously unrecognized cause of renal phosphate loss in humans.

Source Information

From INSERM Unité 845, Université Paris Descartes, Faculté de Médecine (Z.K., N.B., R.A., C.L., L.B., G.P., P.U.-T., G.F., D.P.); Hôpital Bichat–Claude Bernard (B. Gérard, C.S., B. Grandchamp), Hôpital Necker–Enfants Malades (P.U.-T., G.F., D.P.), and Hôpital Européen Georges Pompidou (G.F.), Assistance Publique–Hôpitaux de Paris; and INSERM Unité 773, Unité de Formation et de Recherche Médicale (C.S.), and Institut Fédératif de Recherche 02, INSERM (B. Grandchamp), Université Paris Diderot — all in Paris; and Clinique du Landy, Saint Ouen, France (P.U.-T.).

Drs. Friedlander and Prié contributed equally to this article.

Address reprint requests to Dr. Prié at Service d'Explorations Fonctionnelles, Hôpital Necker–Enfants Malades, 149 Rue de Sèvres, Paris 75015, France, or at prie{at}necker.fr.

Full Text of this Article

Related Letters:

NHERF1 Mutations and Responsiveness of Renal Parathyroid Hormone
Bergwitz C., Bastepe M., Rendina D., De Filippo G., Strazzullo P., Prié D., Friedlander G.
Extract | Full Text | PDF  
N Engl J Med 2008; 359:2615-2617, Dec 11, 2008. Correspondence

This article has been cited by other articles:

• Bergwitz, C., Bastepe, M., Rendina, D., De Filippo, G., Strazzullo, P., Prie, D., Friedlander, G. (2008). NHERF1 Mutations and Responsiveness of Renal Parathyroid Hormone. NEJM 359: 2615-2617 [Full Text]  
• Levi, M., Bruesegem, S. (2008). Renal Phosphate-Transporter Regulatory Proteins and Nephrolithiasis. NEJM 359: 1171-1173 [Full Text]