Effect of variations in dietary Pi intake on intestinal Pi transporters (NaPi-IIb, PiT-1, and PiT-2) and phosphate-regulating factors (PTH, FGF-23, and MEPE).

Hyperphosphatemia is a common condition in patients with chronic kidney disease (CKD) and can lead to bone disease, vascular calcification, and increased risks of cardiovascular disease and mortality. Inorganic phosphate (P) is absorbed in the intestine, an important step in the maintenance of homeostasis. In CKD, it is not clear to what extent P absorption is modulated by dietary P. Thus, we investigated 5/6 nephrectomized (Nx) Wistar rats to test whether acute variations in dietary P concentration over 2 days would alter hormones involved in P metabolism, expression of sodium-phosphate cotransporters, apoptosis, and the expression of matrix extracellular phosphoglycoprotein (MEPE) in different segments of the small intestine. The animals were divided into groups receiving different levels of dietary phosphate: low (Nx/LP), normal (Nx/NP), and high (Nx/HP). Serum phosphate, fractional excretion of phosphate, intact serum fibroblast growth factor 23 (FGF-23), and parathyroid hormone (PTH) were significantly higher and ionized calcium was significantly lower in the Nx/HP group than in the Nx/LP group. The expression levels of NaPi-IIb and PiT-1/2 were increased in the total jejunum mucosa of the Nx/LP group compared with the Nx/HP group. Modification of P concentration in the diet affected the apoptosis of enterocytes, particularly with P overload. MEPE expression was higher in the Nx/HP group than in the Nx/NP. These data reveal the importance of early control of P in uremia to prevent an increase in serum PTH and FGF-23. Uremia may be a determining factor that explains the expressional modulation of the cotransporters in the small intestine segments.