Changes in microparticle profiles by vitamin D receptor activation in chronic kidney disease – a randomized trial

Abstract

Background Microparticles (MPs) are biomarkers and mediators of disease through their expression of surface receptors, reflecting activation or stress in their parent cells. Endothelial markers, ICAM-1 and VCAM-1, are implicated in atherosclerosis and associated with cardiovascular risk. Chronic kidney disease (CKD) patients have endothelial dysfunction and high levels of endothelial derived MPs. Vitamin D treatment has been reported to ameliorate endothelial function in CKD patients. We aimed to examine cell specific MP profiles and concentrations of MPs expressing the atherosclerotic markers ICAM-1 and VCAM-1 after treatment with paricalcitol in patients with CKD stage 3–4. Methods Sub-study of the previously reported SOLID trial where 36 patients were randomly assigned to placebo, 1 or 2 μg paricalcitol, for 12 weeks. MPs were measured by flow cytometry after labelling with antibodies against endothelial (CD62E), platelet (CD62P, CD41, CD154) leukocyte (CD45) and vascular (CD54, CD106) markers. Results Patients had a mean age of 65 years with a mean eGFR of 40 mL/min/1.73m 2 . Concentrations of ICAM-1 positive MPs were significantly reduced by treatment (repeated measures ANOVA p = 0.04). Repeated measures MANOVA of concentrations of endothelial, platelet and leukocyte MPs showed sustained levels in the 2 μg treatment group ( p = 0.85) but a decline in the 1 μg ( p = 0.04) and placebo groups ( p = 0.005). Conclusions Treatment with paricalcitol reduces concentrations of ICAM-1 positive MPs. This is accompanied by sustained concentrations of all cell specific MPs in the 2 μg group, and decreasing concentrations in the other groups, possibly due to a more healthy and reactive endothelium with paricalcitol treatment.

CD40/CD40L Signaling as a Promising Therapeutic Target for the Treatment of Renal Disease

“…Mörtberg and colleagues have recently shown that circulating concentrations of PMPs expressing CD40 ligand were positively associated with the severity of chronic kidney disease, and the concentration of CD40 ligand + PMPs is inversely correlated with estimated glomerular filtration rate (eGFR) [35]. In other studies, CD40 ligand + PMPs of CKD patients can be reduced by the vitamin D2 derivative, paricalcitol [36], or lipid-lowering treatment (LLT) with simvastatin in the settings of diabetes mellitus (DM)-CKD [34].…”

Malnutrition and Biomarkers: A Journey through Extracellular Vesicles

“…Researchers studying the transport mechanisms used by myokines to reach the bloodstream have suggested that they are transported by EVs [ 88 ]. This makes sense, as it is known that the muscle, like any other tissue in the body, releases EVs in the course of pathological conditions such as cancer [ 89 ], HIV [ 90 ], heart attacks [ 91 ], and kidney disease [ 92 ], or due to specific stimulus such as exercise [ 93 ]. Some authors have even suggested that the beneficial health effects that occur as a result of exercising are due to the content of myokines and miRNAs, among others, which are produced by muscle cells and transported via EVs [ 94 , 95 ].…”

A Potential Role of Vitamin D on Platelet Leukocyte Aggregation and Pathological Events in Sepsis: An Updated Review

“…Treatment of an activated (inflamed) endothelial cell line with VD suppresses gene expression for tissue factors and adhesion molecules. 122 Furthermore, treatment with VD in patients with chronic kidney disease who have endothelial dysfunction with high serum levels of circulating microparticles leads to a significant reduction in the level of microparticles; 123 it has also been found to inhibit microparticle release from a human endothelial cell line after their exposure to oxidative stress. 124 Moreover, supplementing high doses of VD decreases thrombin production in severely VD deficient patients.…”