NHERF1Mutations and Responsiveness of Renal Parathyroid Hormone
- 11 September 2008
- journal article
- research article
- Published by Massachusetts Medical Society in New England Journal of Medicine
- Vol. 359 (11), 1128-1135
- https://doi.org/10.1056/nejmoa0802836
Abstract
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.This publication has 22 references indexed in Scilit:
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