Effects of the administration of 25(OH) vitamin D3 in an experimental model of chronic kidney disease in animals null for 1- Alpha-hydroxylase
2017
The final step in vitamin D activation is catalyzed by 1-alpha-hydroxylase (CYP27B1).
Chronic kidney disease (CKD) is characterized by low levels of both 25(OH)D3 and 1,25
(OH)2D3 provoking secondary hyperparathyroidism (2HPT). Therefore, treatments with
active or native vitamin D compounds are common in CKD to restore 25(OH)D3 levels and
also to decrease PTH. This study evaluates the dose of 25(OH)D3 that restores parathyroid
hormone (PTH) and calcium levels in a model of CKD in CYP27B1-/- mice. Furthermore, we
compare the safety and efficacy of the same dose in CYP27B1+/+ animals. The dose
needed to decrease PTH levels in CYP27B1-/- mice with CKD was 50 ng/g. That dose
restored blood calcium levels without modifying phosphate levels, and increased the
expression of genes responsible for calcium absorption (TRPV5 and calbindinD- 28K in the
kidney, TRPV6 and calbindinD-9k in the intestine). The same dose of 25(OH)D3 did not
modify PTH in CYP27B1+/+ animals with CKD. Blood calcium remained normal, while phosphate
increased significantly. Blood levels of 25(OH)D3 in CYP27B1-/- mice were extremely
high compared to those in CYP27B1+/+ animals. CYP27B1+/+ animals with CKD showed
increases in TRPV5, TRPV6, calbindinD-28K and calbindinD-9K, which were not further elevated
with the treatment. Furthermore, CYP27B1+/+ animals displayed an increase in vascular
calcification. We conclude that the dose of 25(OH)D3 effective in decreasing PTH levels
in CYP27B1-/- mice with CKD, has a potentially toxic effect in CYP27B1+/+ animals with
CKD.
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