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dc.contributor.authorTorremadé Pascual, Noèlia
dc.contributor.authorBozić Stanojević, Milica
dc.contributor.authorGoltzman, David
dc.contributor.authorFernández i Giráldez, Elvira
dc.contributor.authorValdivielso Revilla, José Manuel
dc.description.abstractThe 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.sponsorshipThis work was supported by the Instituto de Salud Carlos III PS12/01770, RD12/0021/0026.ca_ES
dc.publisherPublic Library of Scienceca_ES
dc.relation.isformatofReproducció del document publicat a
dc.relation.ispartofPlos One, 2017, vol. 12, núm. 1, e0170654ca_ES
dc.rightscc-by (c) Torremadé et al., 2017ca_ES
dc.titleEffects of the administration of 25(OH) vitamin D3 in an experimental model of chronic kidney disease in animals null for 1- Alpha-hydroxylaseca_ES

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