Paricalcitol reduces oxidative stress and inflammation in hemodialysis patients

Abstract

BackgroundTreatment with selective vitamin D receptor activators such as paricalcitol have been shown to exert an anti-inflammatory effect in patients on hemodialysis, in addition to their action on mineral metabolism and independently of parathyroid hormone (PTH) levels. The objective of this study was to evaluate the additional antioxidant capacity of paricalcitol in a clinical setting.MethodsThe study included 19 patients with renal disease on hemodialysis, of whom peripheral blood was obtained for analysis at baseline and three months after starting intravenous paricalcitol treatment. The following oxidizing and inflammatory markers were quantified: malondialdehyde (MDA), nitrites and carbonyl groups, indoleamine 2,3-dioxygenase (IDO), tumor necrosis factor alfa (TNF-α), interleukin-6 (IL-6), interleukin-18 (IL-18) and C-reactive protein (CRP). Of the antioxidants and anti-inflammatory markers, superoxide dismutase (SOD), catalase, reduced glutathione (GSH), thioredoxin, and interleukin-10 (IL-10) levels were obtained.ResultsBaseline levels of oxidation markers MDA, nitric oxide and protein carbonyl groups significantly decreased after three months on paricalcitol treatment, while levels of GSH, thioredoxin, catalase and SOD activity significantly increased. After paricalcitol treatment, levels of the inflammatory markers CRP, TNF-α, IL-6 and IL-18 were significantly reduced in serum and the level of anti-inflammatory cytokine IL-10 was increased.ConclusionsIn renal patients undergoing hemodialysis, paricalcitol treatment significantly reduces oxidative stress and inflammation, two well known factors leading to cardiovascular damage.

Paricalcitol modulates ACE2 shedding and renal ADAM17 in NOD mice beyond proteinuria

“…In concordance with our findings, a recent study that used rats with a phenotype that resembles type 2 diabetes describes a reduction in oxidative stress and renal lesions when animals were treated with the active vitamin D analog maxacalcitol (28). Furthermore, the antioxidant role of paricalcitol administration also has been described in other experimental models and clinical studies (14,16).…”

Paricalcitol may improve oxidative DNA damage on experimental amikacin-induced nephrotoxicity model

“…We believe that this finding may have important implications for new therapeutic interventions in amikacin-induced nephrotoxicity. Izquierdo et al 32 reported that paricalcitol reduces oxidative stress and inflammation in hemodialysis patients. Furthermore, paricalcitol has been shown to attenuate contrast-induced nephropathy by suppression of renal and systemic oxidative stress.…”

Effects of Paricalcitol and Aliskiren Combination Therapy on Experimental Diabetic Nephropathy Model in Rats

“…Oxidative stress refers to the imbalance between the antioxidative defense system and the oxidative system [26,27]. Recently, it is documented that paricalcitol has not only renin inhibitor effects, but also antioxidant effects [12,28,29,30]. Izquierdo et al reported that paricalcitol decreases serum MDA levels and increases serum GSH, thioredoxin, catalase and SOD activities in hemodialysis patients [29].…”

“…Recently, it is documented that paricalcitol has not only renin inhibitor effects, but also antioxidant effects [12,28,29,30]. Izquierdo et al reported that paricalcitol decreases serum MDA levels and increases serum GSH, thioredoxin, catalase and SOD activities in hemodialysis patients [29]. Similarly, Husain et al reported that paricalcitol and enalapril combination treatment inhibits the increase in cardiac MDA levels and reduces cardiac SOD activity in uremic rats [12].…”