4.1 Article

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

Journal

JOURNAL OF CLINICAL PHARMACOLOGY
Volume 53, Issue 4, Pages 421-426

Publisher

WILEY
DOI: 10.1002/jcph.19

Keywords

gene expression; hemodialysis; inflammation; paricalcitol; peripheral blood mononuclear cells

Funding

  1. Spanish Society of Nephrology
  2. ACINEF
  3. Programa de Intensificacion de la Actividad Investigadora (ISCIII/Comunidad Autonoma de Canarias)

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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.

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