Anti-Inflammatory Profile of Paricalcitol in Hemodialysis Patients: A Prospective, Open-Label, Pilot Study

被引:28
|
作者
Navarro-Gonzalez, Juan F. [1 ,2 ]
Donate-Correa, Javier [2 ]
Mendez, Maria L. [1 ]
Muros de Fuentes, Mercedes
Garcia-Perez, Javier [1 ]
Mora-Fernandez, Carmen [2 ,3 ]
机构
[1] Univ Hosp Nuestra Senora Candelaria, Serv Nephrol, Santa Cruz De Tenerife 38010, Spain
[2] Univ Hosp Nuestra Senora Candelaria, Res Unit, Santa Cruz De Tenerife 38010, Spain
[3] Univ Hosp Nuestra Senora Candelaria, Clin Biochem Serv, Santa Cruz De Tenerife 38010, Spain
来源
JOURNAL OF CLINICAL PHARMACOLOGY | 2013年 / 53卷 / 04期
关键词
gene expression; hemodialysis; inflammation; paricalcitol; peripheral blood mononuclear cells; MESSENGER-RNA EXPRESSION; CHRONIC KIDNEY-DISEASE; D-RECEPTOR ACTIVATORS; NECROSIS-FACTOR-ALPHA; VITAMIN-D; INFLAMMATORY MECHANISMS; VASCULAR CALCIFICATION; CYTOKINE NETWORK; CALCITRIOL; ATHEROSCLEROSIS;
D O I
10.1002/jcph.19
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Inflammation is a strong predictor of increased morbidity and mortality in hemodialysis (HD) patients. Paricalcitol, a selective vitamin D receptor activator used for prevention and treatment of secondary hyperparathyroidism, has shown anti-inflammatory properties in experimental studies, although clinical data are scarce. In an open-label, prospective, single center, pilot study, 25 stable HD patients, previously receiving calcitriol, completed 12 weeks of therapy with oral paricalcitol. Serum and peripheral blood mononuclear cell (PBMC) expression profiles of inflammatory cytokines were analyzed. Serum interleukin (IL)-1, IL-10, and IL-18 did not change, unlike high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor- (TNF-), and IL-6, which experienced a significant mean percent decrease of 14.3%, 4.7%, and 5%, respectively. There was a significant reduction in the TNF-/IL-10 and the IL-6/IL-10 ratios (P<.05). Serum intact parathyroid hormone concentration experienced a mild but significant reduction. In addition, expression levels of TNF- and IL-6 decreased by 19.1% (P<.01) and 17.5% (P<.001), respectively, whereas expression of IL-10 increased by 17.7% (P<.01) after treatment. In conclusion, paricalcitol administration to HD patients is associated with a beneficial effect on the inflammatory cytokine serum and gene expression profile of PBMC. This effect may contribute to the survival benefits of paricalcitol observed in clinical studies.
引用
收藏
页码:421 / 426
页数:6
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