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.