Journal
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
Volume 470, Issue 4, Pages 623-632Publisher
SPRINGER
DOI: 10.1007/s00424-018-2111-6
Keywords
Intestinal absorption; Sodium-phosphate cotransporters; Apoptosis; MEPE; Uremia
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Funding
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (Sao Paulo State Research Foundation) [2011/00036-0]
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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-i) is absorbed in the intestine, an important step in the maintenance of homeostasis. In CKD, it is not clear to what extent P-i absorption is modulated by dietary P-i. Thus, we investigated 5/6 nephrectomized (Nx) Wistar rats to test whether acute variations in dietary P-i concentration over 2 days would alter hormones involved in P-i 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/LPi), normal (Nx/NPi), and high (Nx/HPi). 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/HPi group than in the Nx/LPi group. The expression levels of NaPi-IIb and PiT-1/2 were increased in the total jejunum mucosa of the Nx/LPi group compared with the Nx/HPi group. Modification of P-i concentration in the diet affected the apoptosis of enterocytes, particularly with P-i overload. MEPE expression was higher in the Nx/HPi group than in the Nx/NPi. These data reveal the importance of early control of P-i 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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