Different effects of 22-oxacalcitriol and calcitriol on the course of experimental chronic renal failure.
Calcitriol, 1,25(OH)(2)D(3), has been reported to have a beneficial effect on bone histology in patients with predialysis chronic renal failure; however, such treatment involves a risk of hypercalcemia. To investigate the effects of 1,25(OH)(2)D(3) and 22-oxacalcitriol (OCT) on the progression of histologic deterioration, we administered intraperitoneal 1,25(OH)(2)D(3) or OCT, three times a week, to rats with adriamycin-induced progressive renal failure, from the 10th week after the induction of ADR-induced nephropathy. The rats were divided into the following groups: (1) high-dose 1,25(OH)(2)D(3), 0.2 microg/kg (group D(3)-0.2); (2) low-dose 1,25(OH)(2)D(3), 0.04 microg/kg (group D(3)-0.04); (3) high-dose OCT, 0.2 microg/kg (group OCT-0.2); (4) low-dose OCT, 0.04 microg/kg (group OCT-0.04); and (5) ADR-induced nephropathy (group ADR). The death rate at week 20 in group D(3)-0.2 was 50%, significantly higher than the death rates in the other groups, except for group D(3)-0.04 (P <.05). The serum creatinine and blood urea nitrogen levels were the highest in group D(3)-0.2, although the difference was not significant. In contrast, in groups OCT-0.2 and OCT-0.04, tubular changes and interstitial volume were smaller than in groups D(3)-0.2 and D(3)-0.04 (P <.05). Although calcium deposits increased in group D(3)-0.2, the difference was not significant. Glomerular expression of transforming growth factor-beta1 (TGF-beta1) expression was less in groups OCT-0.2 and OCT-0.04 than in groups D(3)-0.2 and D(3)-0.04 (P <.05). Glomerular fibronectin expression was less in group OCT-0.2 than in groups D(3)-0.2 and ADR (P <.05). Tubulointerstitial expression of TGF-beta1 was greater in group D(3)-0.2 than in group ADR and greater in group D(3)-0.04 than in group OCT-0.04 (P <.05). We conclude that a high dose of 1,25(OH)(2)D(3) accelerated the progressive renal deterioration of ADR-induced nephropathy, and, as a result, OCT was able to attenuate renal histologic lesions.
Sanai
Toru
T
Division of Nephrology and Clinical Research Institute, Department of Internal Medicine, National Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka-city, Fukuoka 810-8563, Japan. hdroom@qmed.hosp.go.jp
Tokumoto
Masanori
M
Hirano
Tadashi
T
Okuda
Seiya
S
D000818:Animals; D015519:Bone Density / Q000187:drug effects; D002117:Calcitriol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000633:toxicity; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000633:toxicity; D005923:Glomerulosclerosis, Focal Segmental / Q000517:prevention & control; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D004317:Doxorubicin; D002117:Calcitriol; C051883:maxacalcitol