title: 22-Oxacalcitriol prevents progressive glomerulosclerosis without adversely affecting calcium and phosphorus metabolism in subtotally nephrectomized rats.
abstract: BACKGROUND
  22-Oxacalcitriol (OCT), an analogue of vitamin D, has been shown to inhibit cell proliferation in cultured mesangial cells. OCT also prevented albuminuria and glomerular injury in an acute model of anti-Thy1 glomerulonephritis. However, potential side effects, including calcaemic actions and tubular dysfunction, of chronic OCT treatment remain unclear. In the present study, we evaluated the effect of OCT in a chronic model of progressive glomerulosclerosis in subtotally nephrectomized (SNX) rats.
  
  
  METHODS
  At one week after subtotal nephrectomy, SNX rats were divided into 3 groups having equivalent serum creatinine levels and body weight. OCT (0.08 or 0.4 micro g/kg body weight) was administered intravenously three times per week for 8 weeks to SNX rats. We evaluated effects of OCT on renal function during treatment and on morphologic parameters in glomeruli at 8 weeks. We additionally measured calcium and phosphate levels in serum and urine, and tubular dysfunction markers, including beta(2)-microgloblin (beta(2)m) and N-acetyl-beta-D-glycosaminidase (NAG) levels in urine.
  
  
  RESULTS
  OCT treatment significantly suppressed urinary albumin excretion, prevented increases in serum creatinine and serum urea nitrogen, and inhibited glomerular cell number, glomerulosclerosis ratio and glomerular volume in SNX rats at 8 weeks. At that time, OCT-treated groups did not show hypercalcaemia, hypercalciuria or hyperphosphaturia. Furthermore, OCT treatment did not affect beta(2)m or NAG levels in urine, and did not induce histological changes in tubular or interstitial regions.
  
  
  CONCLUSIONS
  These findings suggest that OCT may provide a clinically useful agent for preventing the progression of glomerulosclerosis without adversely affecting calcium and phosphorus metabolism or causing subsequent tubular dysfunction.
authors.affiliation: Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co. Ltd, Shizuoka, Japan. hiratamcn@chugai-pharm.co.jp
authors.forename: Michinori
authors.initials: M
authors.lastname: Hirata
authors.forename: Kojiro
authors.initials: K
authors.lastname: Makibayashi
authors.forename: Kyoko
authors.initials: K
authors.lastname: Katsumata
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Kusano
authors.forename: Takeshi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Naoshi
authors.initials: N
authors.lastname: Fukushima
authors.forename: Toshio
authors.initials: T
authors.lastname: Doi
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D003404:Creatinine / Q000097:blood; D018450:Disease Progression; D005923:Glomerulosclerosis, Focal Segmental / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D007678:Kidney Glomerulus / Q000473:pathology; D007684:Kidney Tubules / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009392:Nephrectomy / Q000379:methods; D010758:Phosphorus / Q000378:metabolism*; D011507:Proteinuria / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C035465:22-ketocholesterol; D010758:Phosphorus; D002784:Cholesterol; D003404:Creatinine; D002118:Calcium