Antialbuminuric actions of calcilytics in the remnant kidney

作者：Takenaka Tsuneo^*; Inoue Tsutomu; Miyazaki Takashi; Nishiyama Akira; Ishii Naohito; Hayashi Matsuhiko; Suzuki Hiromichi

来源：American Journal of Physiology - Renal Fluid and Electrolyte Physiology, 2015, 309(3): F216-F226.

DOI：10.1152/ajprenal.00003.2015

• calcium-sensing receptor
• phosphate
• vitamin D
• klotho
• transient receptor potential channel 6

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 Ca2+ 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.

• 出版日期2015-8-1