Evidence for a signaling axis by which intestinal phosphate rapidly modulates renal phosphate reabsorption

Theresa Berndt, Leslie F. Thomas, Theodore A. Craig, Stacy Sommer, Xujian Li, Eric J. Bergstralh, Rajiv Kumar

Research output: Contribution to journalArticle

116 Scopus citations

Abstract

The mechanisms by which phosphorus homeostasis is preserved in mammals are not completely understood. We demonstrate the presence of a mechanism by which the intestine detects the presence of increased dietary phosphate and rapidly increases renal phosphate excretion. The mechanism is of physiological relevance because it maintains plasma phosphate concentrations in the normal range after ingestion of a phosphate-containing meal. When inorganic phosphate is infused into the duodenum, there is a rapid increase in the renal fractional excretion of phosphate (FE Pi). The phosphaturic effect of intestinal phosphate is specific for phosphate because administration of sodium chloride does not elicit a similar response. Phosphaturia after intestinal phosphate administration occurs in thyro-parathyroidectomized rats, demonstrating that parathyroid hormone is not essential for this effect. The increase in renal FE Pi in response to the intestinal administration of phosphate occurs without changes in plasma concentrations of phosphate (filtered load), parathyroid hormone, FGF-23, or secreted frizzled related protein-4. Denervation of the kidney does not attenuate phosphaturia elicited after intestinal phosphate administration. Phosphaturia is not elicited when phosphate is instilled in other parts of the gastrointestinal tract such as the stomach. Infusion of homogenates of the duodenal mucosa increases FE Pi, which demonstrates the presence of one or more substances within the intestinal mucosa that directly modulate renal phosphate reabsorption. Our experiments demonstrate the presence of a previously unrecognized phosphate gut-renal axis that rapidly modulates renal phosphate excretion after the intestinal administration of phosphate.

Original languageEnglish (US)
Pages (from-to)11085-11090
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number26
DOIs
StatePublished - Jun 26 2007

Keywords

  • 1,25-dihydroxyvitamin D
  • FGF-23
  • Fractional excretion of phosphate
  • Intestinal phosphate absorption
  • Secreted frizzled related protein-4

ASJC Scopus subject areas

  • General

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