%0 Journal Article
%T Selective Vitamin D Receptor Activation as Anti-Inflammatory Target in Chronic Kidney Disease
%A J. Donate-Correa
%A V. Dom¨ªnguez-Pimentel
%A M. L. M¨¦ndez-P¨¦rez
%A M. Muros-de-Fuentes
%A C. Mora-Fern¨¢ndez
%A E. Mart¨ªn-N¨²£¿ez
%A V. Caza£¿a-P¨¦rez
%A J. F. Navarro-Gonz¨¢lez
%J Mediators of Inflammation
%D 2014
%I Hindawi Publishing Corporation
%R 10.1155/2014/670475
%X 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£¿m2 and an intact parathyroid hormone (PTH) level higher than 110£¿pg/mL received oral paricalcitol (1£¿¦Ìg/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%, ), TNF-¦Á (11.9%, ), and IL-6 (7%, ), with a nonsignificant increase of IL-10 by 16%. In addition, mRNA expression levels of the TNF¦Á and IL-6 genes in peripheral blood mononuclear cells decreased significantly by 30.8% ( ) and 35.4% ( ), respectively. In conclusion, selective VDR activation is an effective target to modulate inflammation in CKD. 1. Introduction Cardiovascular (CV) disease (CVD) is a very common feature in patients suffering from chronic kidney disease (CKD), particularly in those with end-stage renal disease (ESRD). The elevated CV morbidity and mortality in this population are not completely explained by the classical CV risk factors [1]. Nontraditional CV risk factors are essential elements in the spectrum of CVD in the renal patient, with a great relevance for the role of inflammation and the disturbances of mineral metabolism, which are already evident in the early stages of CKD [2, 3]. Both alterations contributed to the increased CV risk observed in CKD patients with secondary hyperparathyroidism, a frequent complication resulting from the loss of the ability of the kidney to regulate phosphatemia and synthesize calcitriol, the active form of vitamin D [4¨C6]. In the last decade, one of the most relevant therapeutic innovations in the field of CKD has been the introduction of paricalcitol (19-nor-1,25-dihydroxyvitamin D2), a selective activator of the vitamin D receptor for the prevention and treatment of secondary hyperparathyroidism [7, 8]. Paricalcitol has been related to a survival advantage in long-term
%U http://www.hindawi.com/journals/mi/2014/670475/