Phosphate homeostasis and the renal-gastrointestinal axis

Abstract

Transport of phosphate across intestinal and renal epithelia is essential for normal phosphate balance, yet we know less about the mechanisms and regulation of intestinal phosphate absorption than we do about phosphate handling by the kidney. Recent studies have provided strong evidence that the sodium-phosphate cotransporter NaPi-IIb is responsible for sodium-dependent phosphate absorption by the small intestine, and it might be that this protein can link changes in dietary phosphate to altered renal phosphate excretion to maintain phosphate balance. Evidence is also emerging that specific regions of the small intestine adapt differently to acute or chronic changes in dietary phosphate load and that phosphatonins inhibit both renal and intestinal phosphate transport. This review summarizes our current understanding of the mechanisms and control of intestinal phosphate absorption and how it may be related to renal phosphate reabsorption; it also considers the ways in which the gut could be targeted to prevent, or limit, hyperphosphatemia in chronic and end-stage renal failure.

Renal Control of Calcium, Phosphate, and Magnesium Homeostasis

“…As the GFR falls, free serum calcium levels fall and serum phosphorus increases (21). The decrease in free serum calcium and increase in serum phosphorus stimulate the parathyroid glands to produce PTH, which decreases the abundance of Npt2a and Npt2c in the renal proximal tubule, leading to increased Pi excretion in the urine that in turn lowers serum Pi levels ( Figure 6).…”

Recovery of rainbow trout (Oncorhynchus mykiss) after subchronic nitrite exposure

“…One result of stress-related hyperglycaemia is a decrease in food intake, and this could subsequently lead to decreased intensity of nitrogen metabolism. This hypothesis is supported by the changes in inorganic phosphorus concentration, as one of the major determinants of plasma phosphorus concentration is dietary intake as along with gastrointestinal absorption (Marks et al 2010).…”

The SLC34 family of sodium-dependent phosphate transporters

“…The concentration of intracellular inorganic phosphate may be in the range of 0.7 -2.5 mM as determined by 31 The extracellular concentration of phosphate depends to a large extent on mechanisms that control renal excretion of phosphate. Renal handling of phosphate, and to a lesser extent gastrointestinal absorption of phosphate, is controlled by complex regulatory networks that involve several organs and several endocrine factors [20,38,88,96,98].…”

“…Phosphate absorption along the gastrointestinal tract is mediated by two pathways, a transcellular absorptive component, that involves SLC34 and SLC20 sodium-dependent phosphate cotransporters [54, 96,118] and a concentration-or load-dependent absorptive component that may permeate the paracellular route, that, however, is poorly characterized. Together these two processes results in an overall fractional absorption of phosphate that ranges between 65% and 70% of the amount ingested.…”

“…Notably, segmental distribution of absorption of phosphate varies among different species. In humans and rats most of the ingested phosphate is absorbed in duodenum and jejunum, whereas in mice, most of the phosphate absorption occurs in the ileum [96][97]114]. The role of the colon is uncertain.…”