Department of Cardiology, Danderyd University Hospital, 182 88, Stockholm, Sweden.
Department of Clinical Sciences, Danderyd University Hospital, Karolinska Institutet, Stockholm, Sweden.
BMC Nephrol. 2019 Aug 1;20(1):290. doi: 10.1186/s12882-019-1445-4.
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.
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.
Patients had a mean age of 65 years with a mean eGFR of 40 mL/min/1.73m. 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).
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.
微粒（MPs）通过其表面受体的表达作为疾病的生物标志物和介质，反映其母细胞的激活或应激。内皮标志物 ICAM-1 和 VCAM-1 与动脉粥样硬化有关，并与心血管风险相关。慢性肾脏病（CKD）患者存在内皮功能障碍和高水平的内皮衍生 MPs。已有报道称，维生素 D 治疗可改善 CKD 患者的内皮功能。我们旨在研究 CKD 3-4 期患者接受帕立骨化醇治疗后，细胞特异性 MPs 谱和表达动脉粥样硬化标志物 ICAM-1 和 VCAM-1 的 MPs 浓度。
这是之前报道的 SOLID 试验的子研究，其中 36 名患者被随机分配至安慰剂组、1μg 帕立骨化醇组和 2μg 帕立骨化醇组，治疗 12 周。通过用针对内皮（CD62E）、血小板（CD62P、CD41、CD154）、白细胞（CD45）和血管（CD54、CD106）标志物的抗体标记后，通过流式细胞术测量 MPs。
患者的平均年龄为 65 岁，平均 eGFR 为 40mL/min/1.73m。治疗后 ICAM-1 阳性 MPs 的浓度显著降低（重复测量方差分析 p=0.04）。内皮、血小板和白细胞 MPs 浓度的重复测量 MANOVA 显示，2μg 治疗组的水平持续（p=0.85），但 1μg（p=0.04）和安慰剂组（p=0.005）的水平下降。
帕立骨化醇治疗可降低 ICAM-1 阳性 MPs 的浓度。这伴随着 2μg 组所有细胞特异性 MPs 的浓度持续，而其他组的浓度下降，这可能是由于帕立骨化醇治疗使内皮更健康和更具反应性。
