Effects of the administration of 25(OH) vitamin D3 in an experimental model of chronic kidney disease in animals null for 1- Alpha-hydroxylase
| dc.contributor.author | Torremadé Pascual, Noèlia | |
| dc.contributor.author | Bozic, Milica | |
| dc.contributor.author | Goltzman, David | |
| dc.contributor.author | Fernández i Giráldez, Elvira | |
| dc.contributor.author | Valdivielso Revilla, José Manuel | |
| dc.date.accessioned | 2017-02-22T11:16:31Z | |
| dc.date.available | 2017-02-22T11:16:31Z | |
| dc.date.issued | 2017 | |
| dc.description.abstract | 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. | ca_ES |
| dc.description.sponsorship | This work was supported by the Instituto de Salud Carlos III PS12/01770, RD12/0021/0026. | ca_ES |
| dc.identifier.doi | https://doi.org/10.1371/journal.pone.0170654 | |
| dc.identifier.idgrec | 025661 | |
| dc.identifier.issn | 1932-6203 | |
| dc.identifier.uri | http://hdl.handle.net/10459.1/59301 | |
| dc.language.iso | eng | ca_ES |
| dc.publisher | Public Library of Science | ca_ES |
| dc.relation.isformatof | Reproducció del document publicat a https://doi.org/10.1371/journal.pone.0170654 | ca_ES |
| dc.relation.ispartof | Plos One, 2017, vol. 12, núm. 1, e0170654 | ca_ES |
| dc.rights | cc-by (c) Torremadé et al., 2017 | ca_ES |
| dc.rights.accessRights | info:eu-repo/semantics/openAccess | ca_ES |
| dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
| dc.title | Effects of the administration of 25(OH) vitamin D3 in an experimental model of chronic kidney disease in animals null for 1- Alpha-hydroxylase | ca_ES |
| dc.type | article | ca_ES |
| dc.type.version | publishedVersion | ca_ES |