title: In subtotally nephrectomized rats 22-oxacalcitriol suppresses parathyroid hormone with less risk of cardiovascular calcification or deterioration of residual renal function than 1,25(OH)2 vitamin D3.
abstract: BACKGROUND
  Although it effectively suppresses parathyroid hormone (PTH) secretion, vitamin D [1,25(OH)(2)D(3)] therapy often causes tissue calcification over the long term. In patients on chronic dialysis, cardiovascular calcification is clearly linked to an unfavourable prognosis. In pre-dialysis patients, renal calcification of the kidney leads to the deterioration of renal function.
  
  
  METHODS
  We compared the propensities of 22-oxacalcitriol (OCT), with lesser calcaemic action, and 1,25(OH)(2)D(3) for producing their potential side effects in rats: (i) metastatic calcification of heart and aorta, and (ii) renal dysfunction with nephrocalcinosis, using the same effective doses for hyperparathyroidism. OCT (1.25 and 6.25 micro g/kg) or 1,25(OH)(2)D(3) (0.125 and 0.625 micro g/kg) solutions were administered intravenously to subtotally nephrectomized (SNX) rats three times weekly for 2 weeks.
  
  
  RESULTS
  Despite the suppression of PTH to comparable levels, the calcification of the hearts, aortas and kidneys in the 1,25(OH)(2)D(3)-treated group was significantly greater than in the OCT-treated group. Of interest was that, in the OCT (6.25 micro g/kg) group, the degree of calcification in hearts, aortas and kidneys were distinctly lower than those in the 1,25(OH)(2)D(3) (0.125 micro g/kg) group despite the comparable serum Ca x Pi products. Therefore, there may be different mechanisms behind the calcifications resulting from OCT and 1,25(OH)(2)D(3). Deterioration of renal function, tubular changes, and atypical hyperplasia of proximal tubules associated with calcification were more severe in the 1,25(OH)(2)D(3)-treated group than in the OCT-treated group.
  
  
  CONCLUSIONS
  These results indicate that OCT may be an effective agent for the suppression of PTH with a lesser risk of cardiovascular calcification or deterioration of residual renal function.
authors.affiliation: Fuji Gotemba Research Labs, Chugai Pharmaceutical Co., Ltd, Shizuoka, Japan.
authors.forename: Michinori
authors.initials: M
authors.lastname: Hirata
authors.forename: Kyoko
authors.initials: K
authors.lastname: Katsumata
authors.forename: Koichi
authors.initials: K
authors.lastname: Endo
authors.forename: Naoshi
authors.initials: N
authors.lastname: Fukushima
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ohkawa
authors.forename: Masafumi
authors.initials: M
authors.lastname: Fukagawa
mesh_terms: D000818:Animals; D002114:Calcinosis / Q000139:chemically induced*; D002117:Calcitriol / Q000031:analogs & derivatives / Q000494:pharmacology*; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D002319:Cardiovascular System / Q000187:drug effects; D007668:Kidney / Q000187:drug effects; D007674:Kidney Diseases / Q000139:chemically induced*; D008297:Male; D009392:Nephrectomy; D010281:Parathyroid Hormone / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014815:Vitamins / Q000494:pharmacology*
chemical_list: D010281:Parathyroid Hormone; D014815:Vitamins; D002117:Calcitriol; C051883:maxacalcitol