Takenaka Tsuneo, Inoue Tsutomu, Miyazaki Takashi, Nishiyama Akira, Ishii Naohito, Hayashi Matsuhiko, Suzuki Hiromichi
International University of Health and Welfare, Minato, Tokyo, Japan;
Saitama Medical University, Iruma, Saitama, Japan;
Am J Physiol Renal Physiol. 2015 Aug 1;309(3):F216-26. doi: 10.1152/ajprenal.00003.2015. Epub 2015 May 27.
Hyperphosphatemia accelerates the progression of chronic kidney diseases. In the present study, the effects of ronacaleret, a calcilytic agent, on renal injury were assessed in the following four groups of rats: 5/6-nephrectomized Wistar rats as a control (C group), rats treated with ronacaleret (3 mg·kg(-1)·day(-1); R group), rats treated with calcitriol (30 ng·kg(-1)·day(-1); V group), and rats treated with both ronacaleret and calcitriol (R + V group). Three months later, rats were euthanized under anesthesia, and the remnant kidneys were harvested for analysis. Albuminuria was lower in the R and V groups than in the C group (P < 0.05). Creatinine clearance was elevated in the R and V groups compared with the C group (P < 0.05). Serum Ca(2+) and renal ANG II were higher in the R + V group than in the C group (P < 0.05 for each), and serum phosphate was reduced in the R group compared with the C group (P < 0.05). Fibroblast growth factor-23 was lower in the R group and higher in the V and R + V groups than in the C group. However, parathyroid hormone did not differ significantly among the four groups. Renal klotho expression was elevated in the R and V groups compared with the C group (P < 0.05). The present data indicate that ronacaleret preserves klotho expression and renal function with reductions in serum phosphate and albuminuria in 5/6-nephrectomized rats. Our findings demonstrate that vitamin D prevents declines in klotho expression and renal function, suppressing albuminuria.
高磷血症会加速慢性肾脏病的进展。在本研究中,在以下四组大鼠中评估了钙敏感受体阻滞剂罗纳卡列特对肾损伤的影响:5/6肾切除的Wistar大鼠作为对照组(C组)、接受罗纳卡列特治疗的大鼠(3mg·kg⁻¹·天⁻¹;R组)、接受骨化三醇治疗的大鼠(30ng·kg⁻¹·天⁻¹;V组)以及同时接受罗纳卡列特和骨化三醇治疗的大鼠(R + V组)。三个月后,在麻醉下对大鼠实施安乐死,并摘取残余肾脏进行分析。R组和V组的蛋白尿水平低于C组(P < 0.05)。与C组相比,R组和V组的肌酐清除率升高(P < 0.05)。R + V组的血清Ca²⁺和肾血管紧张素II高于C组(每组P < 0.05),且R组的血清磷酸盐水平低于C组(P < 0.05)。R组的成纤维细胞生长因子-23水平低于C组,V组和R + V组高于C组。然而,四组之间甲状旁腺激素水平无显著差异。与C组相比,R组和V组的肾klotho表达升高(P < 0.05)。目前的数据表明,在5/6肾切除的大鼠中,罗纳卡列特可维持klotho表达和肾功能,同时降低血清磷酸盐和蛋白尿水平。我们的研究结果表明,维生素D可防止klotho表达和肾功能下降,抑制蛋白尿。