title: Antialbuminuric actions of calcilytics in the remnant kidney.
abstract: 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.
authors.affiliation: International University of Health and Welfare, Minato, Tokyo, Japan; takenaka@iuhw.ac.jp.
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Takenaka
authors.affiliation: Saitama Medical University, Iruma, Saitama, Japan;
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Saitama Medical University, Iruma, Saitama, Japan;
authors.forename: Takashi
authors.initials: T
authors.lastname: Miyazaki
authors.affiliation: Kagawa University, Kida, Kagawa, Japan;
authors.forename: Akira
authors.initials: A
authors.lastname: Nishiyama
authors.affiliation: Kitasato University, Sagamihara, Kanagawa, Japan; and.
authors.forename: Naohito
authors.initials: N
authors.lastname: Ishii
authors.affiliation: Keio University, Shinjuku, Tokyo, Japan.
authors.forename: Matsuhiko
authors.initials: M
authors.lastname: Hayashi
authors.affiliation: Saitama Medical University, Iruma, Saitama, Japan;
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D058186:Acute Kidney Injury / Q000473:pathology / Q000517:prevention & control*; D000419:Albuminuria / Q000188:drug therapy*; D000818:Animals; D002130:Calcium Phosphates / Q000378:metabolism; D007189:Indans / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D009392:Nephrectomy; D010666:Phenylpropionates / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D044169:Receptors, Calcium-Sensing / Q000037:antagonists & inhibitors; D012077:Renal Artery / Q000473:pathology; D050052:TRPC Cation Channels / Q000096:biosynthesis; D014807:Vitamin D / Q000627:therapeutic use
chemical_list: D002130:Calcium Phosphates; D007189:Indans; D008565:Membrane Proteins; D010666:Phenylpropionates; D044169:Receptors, Calcium-Sensing; D050052:TRPC Cation Channels; C492145:Trpc6 protein, rat; C113267:nephrin; D014807:Vitamin D; C020243:calcium phosphate; C561716:ronacaleret
keywords: calcium-sensing receptor; klotho; phosphate; transient receptor potential channel 6; vitamin D