Журнал исследований и разработок
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Changes in Plasma Levels of Asymmetric Dimethylarginine in Chronic Kidney Disease Patients Treated for 8 Weeks with the Vitamin D Receptor Agonist Paricalcitol

Amy Barton Pai1, Darren W Grabe, George Eisele, Syed Haqqie, Heena Patel, Alexander J Prokopienko, Thomas D Nolin, Natsuki Kubotera

Objective: We investigated the effect of the vitamin D receptor agonist (VDRA), paricalcitol on biomarkers of endothelial dysfunction in patients with chronic kidney disease (CKD).

Methods: This was an 8-week, randomized, blinded, controlled trial of paricalcitol versus placebo in 40 CKD patients. Serum chemistry, asymmetric dimethyl arginine (ADMA), soluble intracellular adhesion molecule (ICAM), vascular adhesion molecule (VCAM), biomarkers of vascular reactivity (Regulated on activation, normal T cell expressed and secreted (RANTES), vascular endothelial growth factor (VEGF), monocyte chemoattractant protein (MCP-1)) and pro-inflammatory cytokines (interleukin-1(IL-1) interleukin (IL-6), tumor necrosis factor- (TNF)) at baseline, week 4 and week 8.

Results: Paricalcitol treated patients had significant reductions in asymmetric dimethylarginine (ADMA) serum concentrations after 4 weeks of treatment. There were no statistically significant changes in mean concentrations of cytokines or biomarkers of endothelial dysfunction among patients receiving paricalcitol or placebo. However, more than one-third of patients receiving paricalcitol had reductions in one or more of the analytes measured. Multiple logistic regression analyses showed that higher baseline serum concentrations of native vitamin D (1,25 OH vitamin D) were inversely associated with reduction of VCAM and all three cytokines evaluated.

Conclusion: Data from this pilot study show that VDRA paricalcitol is associated with short-term reductions in ADMA. Larger interventional studies are warranted.