Medical School, Division of Nephrology, Universidade de São Paulo, São Paulo, Brazil.
Department of Anatomy, Institute of Biomedical Sciences, Universidade de São Paulo, São Paulo, Brazil.
Pflugers Arch. 2018 Apr;470(4):623-632. doi: 10.1007/s00424-018-2111-6. Epub 2018 Jan 25.
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.
高磷血症是慢性肾脏病（CKD）患者的常见病症，可导致骨病、血管钙化以及心血管疾病和死亡率增加。无机磷（P）在肠道中被吸收，这是维持体内平衡的重要步骤。在 CKD 中，尚不清楚饮食 P 变化在多大程度上调节 P 吸收。因此，我们研究了 5/6 肾切除（Nx）Wistar 大鼠，以测试在 2 天内急性改变饮食 P 浓度是否会改变参与 P 代谢的激素、钠磷协同转运蛋白的表达、凋亡以及不同肠段中细胞外基质磷糖蛋白（MEPE）的表达。将动物分为接受不同水平饮食磷酸盐的组：低（Nx/LP）、正常（Nx/NP）和高（Nx/HP）。与 Nx/LP 组相比，Nx/HP 组血清磷酸盐、磷酸盐的分数排泄、完整血清成纤维细胞生长因子 23（FGF-23）和甲状旁腺激素（PTH）显著升高，离子钙显著降低。与 Nx/HP 组相比，Nx/LP 组总空肠黏膜中 NaPi-IIb 和 PiT-1/2 的表达水平升高。饮食中 P 浓度的改变影响了肠细胞的凋亡，特别是 P 过载时。Nx/HP 组 MEPE 的表达高于 Nx/NP 组。这些数据揭示了早期控制尿毒症中 P 的重要性，以防止血清 PTH 和 FGF-23 增加。尿毒症可能是解释小肠道段协同转运蛋白表达调节的决定因素。
