Differential effects of oral doxercalciferol (Hectorol) or paricalcitol (Zemplar) in the Cyp27b1-null mouse model of uremia.
Nephron Exp Nephrol
; 119(3): e67-74, 2011.
Article
en En
| MEDLINE
| ID: mdl-21849802
ABSTRACT
BACKGROUND/AIMS:
Kidney disease patients experience declining calcitriol levels and develop secondary hyperparathyroidism (SHPT). Animal models of uremia based on 5/6 nephrectomy (NTX) do not consistently reproduce this calcitriol deficiency. We developed an animal model, the NTX Cyp27b1-null mouse, which completely lacks endogenous calcitriol, and examined the suitability of this model for evaluation of treatment with vitamin D analogs in uremia.METHODS:
NTX was performed at 2 months of age. One week post-NTX, animals were treated for 4 weeks with vehicle; doxercalciferol at 30, 100 or 300 pg/g body weight (b.w.); or paricalcitol at 100, 300 or 1,000 pg/g b.w. by gavage 3 times per week.RESULTS:
Serum blood urea nitrogen and creatinine were elevated. Vehicle-treated NTX null mice had hypocalcemia and SHPT. Doxercalciferol at 100 or 300 pg/g b.w. normalized serum calcium and parathyroid hormone (PTH) levels. Paricalcitol at 300 or 1,000 pg/g normalized serum calcium, but PTH levels remained elevated. Osteomalacia was corrected by 100 pg/g b.w. of doxercalciferol or 1,000 pg/g b.w. of paricalcitol. The highest dose of doxercalciferol, but not of paricalcitol, significantly reduced osteitis fibrosa.CONCLUSION:
Our results reveal the differential efficacy of doxercalciferol and paricalcitol in this novel animal model incorporating both calcitriol deficiency and renal insufficiency.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Uremia
/
Ergocalciferoles
/
25-Hidroxivitamina D3 1-alfa-Hidroxilasa
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Nephron Exp Nephrol
Asunto de la revista:
NEFROLOGIA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Canadá