Vitamin D receptor activation reduces inflammatory cytokines and plasma MicroRNAs in moderate chronic kidney disease - a randomized trial

Ladan Mansouri, Kristina Lundwall, Ali Moshfegh, Stefan H Jacobson, Joachim Lundahl, Jonas Spaak, Ladan Mansouri, Kristina Lundwall, Ali Moshfegh, Stefan H Jacobson, Joachim Lundahl, Jonas Spaak

Abstract

Background: Chronic kidney disease (CKD) is a major risk factor for cardiovascular disease (CVD), partly due to endothelial dysfunction and chronic inflammation. Vitamin D treatment in end stage renal disease is suggested to modulate the immune system and lead to improved outcomes. We and others have demonstrated that treatment with vitamin D or activated vitamin D analogues protects the endothelial function in less severe renal disease as well. Since the endothelial protection might be mediated by vitamin D effects on inflammation, we assessed levels of pro-inflammatory cytokines and micro RNAs (miRs) in patients with moderate CKD, treated with an active vitamin D analogue (paricalcitol).

Methods: Thirty-six patients with moderate CKD were randomized to 12 weeks treatment with placebo, 1 μg, or 2 μg paricalcitol daily. Cytokines were measured by Milliplex 26-plex. Total RNA was isolated from plasma and miRs were determined by quantitative reverse transcription PCR analysis.

Results: Selected pro-inflammatory cytokines decreased significantly following treatment, while no change was observed in the placebo group. The micro RNAs; miR 432-5p, miR 495-3p, and miR 576-5p were significantly downregulated in the active treated groups, compared to the placebo group.

Conclusion: Paricalcitol treatment for 12 weeks in patients with moderate CKD reduces cytokines and micro RNAs involved in atherosclerosis and inflammation. The potentially protective role of vitamin D receptor activation in the inflammatory processes regarding the long-term outcomes in CKD patients warrants further studies.

Trial registration: SOLID study; NCT01204528 , April 27, 2010.

Keywords: Chronic kidney disease; Endothelial function; Inflammation; Micro RNA; Paricalcitol; VEGF.

Figures

Fig. 1
Fig. 1
Significantly changed plasma microRNAs following treatment, comparing the three groups; placebo, 1 μg and 2 μg. Scatter plots represent 25–75% interquartile range with a line at the median

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