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.

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Hyperphosphatemia is a common and serious complication of chronic kidney disease, contributing to the increased cardiovascular mortality seen in this patient group. The sodium phosphate (P) cotransporters system is involved in intestinal P absorption and is regulated by several factors. We investigate the effect of diets with distinct concentrations of P in the regulation of cotransporters NaPIIb and PiT1 in the intestine of rats. Male Wistar rats (n=66) were used, 33 of which were submitted to nephrectomy 5/6 (Nx) and the others were used as controls (C). The animals received a standard (ST) diet (20% protein and 0.54% P) for 30 days, after they were divided into 2 sets of 3 groups in accordance with the concentration of P in the diet (0.2%, 0.54% or 0.9%) and fed for 2 days. Blood samples, 24h urine, and intestine (duodenum, ileum and jejunum) were accordingly collected. Immunofluorescence, Western blot or ELISA were used to analyze the expressions of the cotransporters and qRT‐PCR to evaluate the gene expression of NaPIIb and PiT1. The concentrations of Cr, Pi, FGF23, PTH and Albu were higher in Nx animals. Pu decreased in Nx animals and some of these parameters were modified by the concentration of dietary P. There were significant differences in the expression of PiT1 in jejunum and ileum of Nx animals in diet 0.2% P relative to their respective controls, normalized to B‐actin (p=0.01 and p=0.02, respectively). The results demonstrate alteration in P homeostasis in Nx animals impaired upregulation of cotransporters in the P low diet and downregulation in the P high diet differently of the controls, as observed in PCR and immunofluorescence for PiT and NaPi in duodenum, respectively. Grant Funding Source: Supported by FAPESP

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