Impact of altered dietary calcium–phosphorus ratio caused by high-phosphorus          diets in a rat chronic kidney disease (CKD) model created by partial ligation of the renal          arteries

Watanabe Atsushi, Koizumi Toshinori, Horikawa Takumi, Sano Yusuke, Uki Haruka, Miyajima Katsuhiro, Kemuriyama Noriko, Anzai Reo, Iwata Hijiri, Anzai Takayuki, Nakagawa Kenshi, Nakae Dai

doi:10.1293/tox.2019-0086

<p> This study aimed to establish a rat chronic kidney disease (CKD) model by studying the effects of a high-phosphorus diet in rats that had undergone partial ligation of the renal arteries (RL). Separate groups of 10-week-old male Slc:Sprague-Dawley rats underwent RL and were fed diets with varying phosphorous levels for a period of 48 days. A marked suppression of body weight gain necessitating humane euthanization occurred on day 28 in rats that had undergone RL and were given high-phosphorus feed. By contrast, the group of intact animals on a high-phosphorus feed exhibited a slightly decreased body weight gain from day 21 and survived until scheduled euthanization. In rats with RL, hematological, blood biochemical, and histopathological analyses demonstrated the presence of CKD-like conditions, particularly in the group that were fed a high-phosphorus diet. Hyperphosphatemia and hypocalcemia were induced by a high-phosphorus diet in both the RL and intact groups, both of which had high levels of FGF23 and parathyroid hormone in the blood. Rats with RL on a high-phosphorus diet showed decreased hematopoiesis by the hematopoietic cell area being narrower in the medullary cavity, proliferation of mesenchymal cells and osteoblasts/osteoclasts, and expansion of the osteoid area, a furthermore generalized vascular lesions, such as calcification, were observed. These findings demonstrate that the partial ligation of the renal arteries combined with a calcium–phosphorus imbalance induced by a high-phosphorus diet serves as an animal model for CKD-like conditions accompanied by bone lesions, helping to elucidate this clinical condition and its underlying molecular mechanisms.</p>

Impact of altered dietary calcium–phosphorus ratio caused by high-phosphorus diets in a rat chronic kidney disease (CKD) model created by partial ligation of the renal arteries

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