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/1.73m2. 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.

• Authors: Kristina Lundwall, Josefin Mörtberg, Fariborz Mobarrez, Stefan H Jacobson, Gun Jörneskog, Jonas Spaak
• Journal: BMC nephrology (BMC Nephrol) Vol. 20 Issue 1 Pg. 290 (08 01 2019) ISSN: 1471-2369 [Electronic] England
• PMID: 31370809 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Ergocalciferols
• ICAM1 protein, human
• Receptors, Calcitriol
• Vascular Cell Adhesion Molecule-1
• Intercellular Adhesion Molecule-1
• paricalcitol

Topics

• Aged
• Aged, 80 and over
• Cell-Derived Microparticles (chemistry, metabolism)
• Double-Blind Method
• Ergocalciferols (pharmacology)
• Female
• Humans
• Intercellular Adhesion Molecule-1 (analysis, biosynthesis)
• Male
• Middle Aged
• Receptors, Calcitriol (drug effects, physiology)
• Renal Insufficiency, Chronic (metabolism)
• Vascular Cell Adhesion Molecule-1 (analysis, biosynthesis)