Lundwall Kristina, Jörneskog Gun, Jacobson Stefan H, Spaak Jonas
Department of Clinical Sciences, Danderyd University Hospital, Karolinska Institutet, Stockholm, Sweden.
Am J Nephrol. 2015;42(4):265-73. doi: 10.1159/000441364. Epub 2015 Oct 24.
Vitamin D deficiency, sympathetic activation and endothelial dysfunction are associated with increased cardiovascular risk in patients with chronic kidney disease (CKD). Studies have so far failed to establish the role of vitamin D and vitamin D receptor activator (VDRA) treatment in moderate CKD. This trial was designed to assess whether VDRA treatment can ameliorate sympathetic activation and macro- and microvascular dysfunction in non-diabetic patients with moderate CKD.
We conducted a randomized controlled double-blind trial using placebo, 1 or 2 μg of paricalcitol, a VDRA, for 3 months. We assessed muscle sympathetic nerve activity (MSNA) by microneurography, pulse wave velocity (PWV) by tonometry, flow mediated vasodilatation (FMD) by brachial ultrasound, skin microcirculation assessed by iontophoresis and capillary blood velocity (CBV) by videophotometric capillaroscopy.
Thirty-six patients with a mean age of 65 years and mean estimated glomerular filtration rate of 40 ml/min/1.73 m2 were included. We found a significant decline in endothelial function after 3 months, except in the group receiving 2 μg of paricalcitol. The higher dose (2 μg) seemed to attenuate the decline in microvascular endothelial function, assessed by iontophoresis of acetylcholine (p=0.06 for all groups, p=0.65 for the 2 μg group) and for FMD (p=0.006 for all groups, p=0.54 for the 2 μg group). We found a borderline significance (p=0.05) for improved CBV in the treated groups. We found no significant changes between treatments in MSNA, PWV or albuminuria.
Endothelial function declined significantly over 3 months in patients with moderate CKD, and this decline could be ameliorated by VDRA treatment (NCT01204528).
维生素D缺乏、交感神经激活和内皮功能障碍与慢性肾脏病(CKD)患者心血管风险增加相关。目前的研究尚未明确维生素D及维生素D受体激动剂(VDRA)治疗在中度CKD中的作用。本试验旨在评估VDRA治疗能否改善非糖尿病中度CKD患者的交感神经激活以及大、微血管功能障碍。
我们进行了一项随机对照双盲试验,使用安慰剂、1或2μg帕立骨化醇(一种VDRA)治疗3个月。我们通过微神经图评估肌肉交感神经活动(MSNA),通过眼压计评估脉搏波速度(PWV),通过肱动脉超声评估血流介导的血管舒张(FMD),通过离子电渗法评估皮肤微循环,通过视频光度毛细血管镜评估毛细血管血流速度(CBV)。
纳入了36例平均年龄65岁、平均估计肾小球滤过率为40 ml/min/1.73 m²的患者。我们发现3个月后内皮功能显著下降,但接受2μg帕立骨化醇治疗的组除外。较高剂量(2μg)似乎减弱了微血管内皮功能的下降,通过乙酰胆碱离子电渗法评估(所有组p = 0.06,2μg组p = 0.65)以及FMD评估(所有组p = 0.006,2μg组p = 0.54)。我们发现治疗组CBV改善具有临界显著性(p = 0.05)。我们发现治疗组之间MSNA、PWV或蛋白尿无显著变化。
中度CKD患者的内皮功能在3个月内显著下降,而VDRA治疗可改善这种下降(NCT01204528)。