Differential Effects of Oral Doxercalciferol (Hectorol (R)) or Paricalcitol (Zemplar (R)) in the Cyp27b1-Null Mouse Model of Uremia

作者：St Arnaud Rene^*; Arabian Alice; Akhouayri Omar; Knutson Joyce C; Strugnell Stephen A

来源：Nephron Experimental Nephrology, 2011, 119(3): E67-E74.

DOI：10.1159/000329663

• Doxercalciferol
• Paricalcitol
• Secondary hyperparathyroidism
• 25-hydroxyvitamin D-1-hydroxylase
• Bone
• Parathyroid hormone

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.

• 出版日期2011