Abstract
BackgroundMicroparticles (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.MethodsSub-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.ResultsPatients 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).ConclusionsTreatment 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.
Highlights
Microparticles (MPs) are biomarkers and mediators of disease through their expression of surface receptors, reflecting activation or stress in their parent cells
Intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) are considered to reflect the level of endothelial proinflammatory and proatherosclerotic activation in the endothelium [50]. This is a sub-study of the SOLID trial in which we show that active vitamin D attenuates a decline in endothelial function measured by flow mediated vasodilatation (FMD), and reduces levels of proinflammatory cytokines [15, 22]
Inclusion criteria were an estimated glomerular filtration rate of 15–59 mL/min/ 1.73m2 (plasma creatinine used in the Modification of Diet in Renal Disease (MDRD) formula), age > 20 years, a calcium level below 2.6 mmol/L, a plasma parathyroid hormone (PTH) level of 3.7–53 pmol/L, a serum albumin above 30 g/L and with no changes in angiotensin converting enzyme inhibitor or angiotensin receptor blocker 2 months before the trial
Summary
Microparticles (MPs) are biomarkers and mediators of disease through their expression of surface receptors, reflecting activation or stress in their parent cells. 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. The importance of the close association between chronic kidney disease (CKD) and cardiovascular disease (CVD), the cardiorenal syndrome, is becoming increasingly recognised among nephrologists and cardiologists [1,2,3]. The mechanisms underlying this association have been explored during the last decade, identifying an accelerated. Regarding measures of arterial stiffness, the step in the vascular disease process, most [27, 28] but not all [10, 11] studies have been negative
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
