title: R-568 reduces ectopic calcification in a rat model of chronic kidney disease-mineral bone disorder (CKD-MBD).
abstract: BACKGROUND
  Chronic kidney disease-mineral bone disorder (CKD-MBD), a newly defined disorder in patients with CKD, describes the interacting triad of (1) biochemical abnormalities of calcium, phosphorus and parathyroid hormone (PTH), (2) extraskeletal calcification and (3) abnormal bone.
  
  
  METHODS
  We studied the effects of the calcimimetic R-568, R-568 with calcium (R-568 + Ca) or calcium (Ca) alone compared with control CKD rats on this triad in the Cy/+ male rat, a model of progressive CKD that spontaneously develops CKD-MBD on a normal phosphorus diet. Animals were treated for either 14 or 18 weeks beginning at 20 weeks of age (34-week and 38-week animals, respectively).
  
  
  RESULTS
  The results demonstrated similar efficacy of R-568, R-568 + Ca and Ca in lowering PTH levels. R-568 alone lowered plasma calcium compared to control over time, but increased phosphorus compared to control early in the course of the disease, but not at 38 weeks. Animals treated with Ca alone or R-568 + Ca had lower phosphorus levels; the Ca alone group had elevated Ca levels. Bone volume improved in the calcium-treated groups. In contrast, arterial and cardiac calcification worsened by most assessments in the R-568 + Ca and Ca alone treated animals compared with R-568 alone whereas R-568 alone treatment showed beneficial effects on most sites of extraskeletal calcification.
  
  
  CONCLUSIONS
  Thus, R-568, with or without Ca, improved the biochemical abnormalities of hyperparathyroidism but with higher and lower calcium levels, respectively, compared with controls. However, R-568 + Ca had more dramatic improvement in bone volume, but more extraskeletal calcification than R-568 alone. This complexity demonstrates that treatment of one component of CKD-MBD may lead to undesirable effects on other components.
authors.affiliation: Indiana University School of Medicine, Roudebush Veterans Affairs Medical Center, Indianapolis, IN, USA. smoe@iupui.edu
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Moe
authors.forename: Mark F
authors.initials: MF
authors.lastname: Seifert
authors.forename: Neal X
authors.initials: NX
authors.lastname: Chen
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Sinders
authors.forename: Xianming
authors.initials: X
authors.lastname: Chen
authors.forename: Dana
authors.initials: D
authors.lastname: Duan
authors.forename: Charles
authors.initials: C
authors.lastname: Henley
authors.forename: Dave
authors.initials: D
authors.lastname: Martin
authors.forename: Vincent H
authors.initials: VH
authors.lastname: Gattone
mesh_terms: D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D002114:Calcinosis / Q000209:etiology / Q000517:prevention & control*; D002118:Calcium / Q000819:agonists / Q000378:metabolism; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000378:metabolism*; D004195:Disease Models, Animal; D006961:Hyperparathyroidism / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008903:Minerals / Q000378:metabolism*; D010627:Phenethylamines; D016891:Polycystic Kidney, Autosomal Dominant / Q000378:metabolism*; D011437:Propylamines; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000814:Aniline Compounds; D008903:Minerals; C107873:N-(2-chlorophenylpropyl)-1-(3-methoxyphenyl)ethylamine; D010627:Phenethylamines; D011437:Propylamines; D002118:Calcium