1.
Exploring the potential effect of paricalcitol on markers of inflammation in de novo renal transplant recipients.
Pihlstrøm, HK, Ueland, T, Michelsen, AE, Aukrust, P, Gatti, F, Hammarström, C, Kasprzycka, M, Wang, J, Haraldsen, G, Mjøen, G, et al
PloS one. 2020;(12):e0243759
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. [NCT01694160 (2012/107D)]; [www.clinicaltrials.gov].
2.
The D-vitamin metabolite 1,25(OH)2 D in serum is associated with disease activity and Anti-Citrullinated Protein Antibodies in active and treatment naïve, early Rheumatoid Arthritis Patients.
Herly, M, Stengaard-Pedersen, K, Vestergaard, P, Østergaard, M, Junker, P, Hetland, ML, Hørslev-Petersen, K, Ellingsen, T
Scandinavian journal of immunology. 2018;(3):e12704
Abstract
RATIONALE Sufficient levels of vitamin D seem to be essential for proper immune function, and low levels might be associated to disease activity in Rheumatoid Arthritis (RA). Most studies investigate only 25OHD and not the physiologically active vitamin D metabolite, 1,25(OH)2 D. OBJECTIVE To investigate associations between serum level of vitamin D metabolites and disease activity parameters in 160 inflammatory active and treatment naïve early RA patients. Serum level of vitamin D metabolites (25OHD2 , 25OHD3 and 1,25(OH)2 D) was measured by isotope dilution mass spectrometry and radio-immunoassays at baseline. Disease characteristics were gender, number of tender joints, number of swollen joints, DAS28-CRP, HAQ, VAS-scores, CRP, erosive status (Total Sharp Score; TSS), ACPA and IgM-RF-status. Associations were evaluated using Spearman's and Wilcoxon rank-sum tests. The study was registered in clinical trials; trial registration number: NCT00209859. FINDINGS Statistically significant inverse associations were found between the active metabolite 1,25(OH)2 D and DAS28-CRP (P = 0.004, rho = -0.23), HAQ (P = 0.005, rho = -0.22), CRP (P = 0.001, rho = -0.25), VASpatient-pain (P = 0.008, rho = -0.21), and a positive association was found to ACPA-status (P = 0.04). CONCLUSION The vitamin D metabolite 1,25(OH)2 D was inversely associated with disease activity and positively associated with ACPA in treatment naïve and inflammatory active early RA. The results indicate that in RA, both the degree of inflammatory activity, and the diagnostic sensitivity and specificity might affect-or might be affected by the level of vitamin 1,25(OH)2 D.
3.
Vitamin D receptor activation reduces inflammatory cytokines and plasma MicroRNAs in moderate chronic kidney disease - a randomized trial.
Mansouri, L, Lundwall, K, Moshfegh, A, Jacobson, SH, Lundahl, J, Spaak, J
BMC nephrology. 2017;(1):161
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.
4.
Vitamin D in organ transplantation.
Stein, EM, Shane, E
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2011;(7):2107-18
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Abstract
Vitamin D deficiency is prevalent among patients with end-stage organ failure awaiting transplant. Low serum 25-hydroxyvitamin D (25-OHD) levels in these patients may be related to many disease-specific factors, as well as decreased sunlight exposure and limited intake of foods containing vitamin D. Low serum 25-OHD levels are also extremely common following solid organ transplantation, both during the immediate postoperative period and in long-term graft recipients. Demographic and lifestyle factors are important in determining D status in transplant recipients. Worse vitamin D status is associated with poorer general health, lower albumin, and even decreased survival among these patients. Although several studies have demonstrated that active forms of vitamin D and its analogues prevent bone loss following transplantation, the data do not show consistent benefit. These therapies may have particular utility after renal transplantation. However, given the narrow therapeutic window with respect to hypercalcemia and hypercalciuria, and the demonstrated efficacy of bisphosphonates to prevent post-transplantation bone loss, we regard these agents as adjunctive rather than primary therapy for transplantation osteoporosis. The effects of 1,25(OH)(2)D on the immune system, which are still being elucidated, may have potential for reducing infections and preventing allograft rejection after transplantation.