title: Selective vitamin D receptor activation as anti-inflammatory target in chronic kidney disease.
abstract: Paricalcitol, a selective vitamin D receptor (VDR) activator used for treatment of secondary hyperparathyroidism in chronic kidney disease (CKD), has been associated with survival advantages, suggesting that this drug, beyond its ability to suppress parathyroid hormone, may have additional beneficial actions. In this prospective, nonrandomised, open-label, proof-of-concept study, we evaluated the hypothesis that selective vitamin D receptor activation with paricalcitol is an effective target to modulate inflammation in CKD patients. Eight patients with an estimated glomerular filtration rate between 15 and 44 mL/min/1.73 m(2) and an intact parathyroid hormone (PTH) level higher than 110 pg/mL received oral paricalcitol (1  μg/48 hours) as therapy for secondary hyperparathyroidism. Nine patients matched by age, sex, and stage of CKD, but a PTH level <110 pg/mL, were enrolled as a control group. Our results show that five months of paricalcitol administration were associated with a reduction in serum concentrations of hs-CRP (13.9%, P < 0.01), TNF-α (11.9%, P = 0.01), and IL-6 (7%, P < 0.05), with a nonsignificant increase of IL-10 by 16%. In addition, mRNA expression levels of the TNFα and IL-6 genes in peripheral blood mononuclear cells decreased significantly by 30.8% (P = 0.01) and 35.4% (P = 0.01), respectively. In conclusion, selective VDR activation is an effective target to modulate inflammation in CKD.
authors: Research Unit, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain ; GEENDIAB (Grupo Español para el Estudio de la Nefropatía Diabética) and REDINREN (RD12/0021/0019), Spain.
authors: J
authors: J
authors: Donate-Correa
authors: Nephrology Service, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain.
authors: V
authors: V
authors: Domínguez-Pimentel
authors: Nephrology Service, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain.
authors: M L
authors: ML
authors: Méndez-Pérez
authors: GEENDIAB (Grupo Español para el Estudio de la Nefropatía Diabética) and REDINREN (RD12/0021/0019), Spain ; Clinical Analysis Service, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain.
authors: M
authors: M
authors: Muros-de-Fuentes
authors: Research Unit, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain ; GEENDIAB (Grupo Español para el Estudio de la Nefropatía Diabética) and REDINREN (RD12/0021/0019), Spain.
authors: C
authors: C
authors: Mora-Fernández
authors: Research Unit, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain.
authors: E
authors: E
authors: Martín-Núñez
authors: Research Unit, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain.
authors: V
authors: V
authors: Cazaña-Pérez
authors: Research Unit, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain ; GEENDIAB (Grupo Español para el Estudio de la Nefropatía Diabética) and REDINREN (RD12/0021/0019), Spain ; Nephrology Service, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain.
authors: J F
authors: JF
authors: Navarro-González
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000737:chemistry*; D016022:Case-Control Studies; D004872:Ergocalciferols / Q000008:administration & dosage; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000188:drug therapy; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D011446:Prospective Studies; D018167:Receptors, Calcitriol / Q000378:metabolism*; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D004872:Ergocalciferols; D010281:Parathyroid Hormone; D018167:Receptors, Calcitriol; C084656:paricalcitol