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Exploring the potential effect of paricalcitol on markers of inflammation in de novo renal transplant recipients

Permanent link
https://hdl.handle.net/10037/20337
DOI
https://doi.org/10.1371/journal.pone.0243759
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Date
2020-12-16
Type
Journal article
Tidsskriftartikkel
Peer reviewed

Author
Pihlstrøm, Hege; Ueland, Thor; Michelsen, Annika; Aukrust, Pål; Gatti, Francesca; Hammarström, Clara Louise; Kasprzycka, Monika; Wang, Junbai; Haraldsen, Guttorm; Mjøen, Geir; Dahle, Dag Olav; Midtvedt, Karsten; Eide, Ivar Anders; Hartmann, Anders; Holdaas, Hallvard
Abstract
Following a successful renal transplantation circulating markers of inflammation may remain elevated, and systemic inflammation is associated with worse clinical outcome in renal transplant recipients (RTRs). Vitamin D-receptor (VDR) activation is postulated to modulate inflammation and endothelial function. We aimed to explore if a synthetic vitamin D, paricalcitol, could influence systemic inflammation and immune activation in RTRs. Newly transplanted RTRs were included in an open-label randomized controlled trial on the effect of paricalcitol on top of standard care over the first post-transplant year. Fourteen pre-defined circulating biomarkers reflecting leukocyte activation, endothelial activation, fibrosis and general inflammatory burden were analyzed in 74 RTRs at 8 weeks (baseline) and 1 year post-engraftment. Mean changes in plasma biomarker concentrations were compared by t-test. The expression of genes coding for the same biomarkers were investigated in 1-year surveillance graft biopsies (n = 60). In patients treated with paricalcitol circulating osteoprotegerin levels increased by 0.19 ng/ml, compared with a 0.05 ng/ml increase in controls (p = 0.030). In graft tissue, a 21% higher median gene expression level of TNFRSF11B coding for osteoprotegerin was found in paricalcitol-treated patients compared with controls (p = 0.026). Paricalcitol treatment did not significantly affect the blood- or tissue levels of any other investigated inflammatory marker. In RTRs, paricalcitol treatment might increase both circulating and tissue levels of osteoprotegerin, a modulator of calcification, but potential anti-inflammatory treatment effects in RTRs are likely very modest.
Publisher
Public Library of Science
Citation
Pihlstrøm, Ueland, Michelsen, Aukrust, Gatti, Hammarström CL, Kasprzycka, Wang, Haraldsen, Mjøen, Dahle, Midtvedt, Eide, Hartmann, Holdaas. Exploring the potential effect of paricalcitol on markers of inflammation in de novo renal transplant recipients. PLOS ONE. 2020;15:e0273059(12):1-14
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