Laboratory of Molecular Medicine, Department of Clinical Immunology, University of Copenhagen, Copenhagen, Denmark.
Department of Cardiology, Herlev Hospital, Herlev, Denmark.
Hemodial Int. 2021 Oct;25(4):479-488. doi: 10.1111/hdi.12948. Epub 2021 Jun 16.
This study aimed to investigate changes in complement system-related molecules in patients undergoing hemodialysis.
Patients >18 years of age on maintenance hemodialysis were included. Using enzyme-linked immunosorbent assays (ELISA) methods complement related molecules ficolin-1, ficolin-2, ficolin-3 mannose-binding lectin, long pentraxin 3, complement activation products C3c, and complement activation potentials were measured before and after a single hemodialysis treatment. All patients were dialyzed with synthetic high flux filters >1.6 m , respectively, Polyamix and Polysulfone, and the Kt/V was maintained >1.3.
Three hundred and four patients were included. There was a modest decrease in plasma level of ficolin-1 (p < 0.001). Ficolin-2 was virtually depleted with median 3.9 (interquartile range [IQR]: 2.6-6.1, range 0.3-13.5) μg/ml before dialysis to median 0.0 (IQR: 0.0-0.5, range 0.0-5.5) μg/ml after dialysis (p < 0.001). No significant difference before and after hemodialysis was seen for mannose-binding lectin and long pentraxin 3 (p > 0.05). In a random subgroup of 160 patients ficolin-2-binding, ficolin-3-mediated lectin pathway capacity and classical pathway capacity were significantly decreased due to hemodialysis. The complement capacity of the alternative pathway was increased after hemodialysis (p = 0.0101), while mannose-binding lectin-mediated lectin pathway capacity was unaltered (p = 0.79). There was an increase in the complement activation product C3c (p < 0.0001), while the concentration of total C4 and C3 did not change (p > 0.158). Multivariate Cox proportional hazard analyses showed an increased risk for all-cause mortality with increasing ficolin-2 (p = 0.002) after hemodialysis.
Plasma ficolin-2 was virtually depleted from the circulation after hemodialysis. However, elevated plasma ficolin-2 levels after hemodialysis was independently associated with increased mortality.
本研究旨在探讨接受血液透析患者补体系统相关分子的变化。
纳入年龄>18 岁的维持性血液透析患者。采用酶联免疫吸附测定（ELISA）方法检测补体相关分子纤维胶素-1、纤维胶素-2、纤维胶素-3 甘露糖结合凝集素、长 pentraxin 3、补体激活产物 C3c 和补体激活潜能，分别在单次血液透析治疗前后进行测量。所有患者均使用>1.6 m 的合成高通量过滤器进行透析，分别为聚酰胺和聚砜，Kt/V 维持在>1.3。
共纳入 304 例患者。纤维胶素-1 的血浆水平略有下降（p<0.001）。纤维胶素-2 在透析前的中位数为 3.9（四分位距 [IQR]：2.6-6.1，范围 0.3-13.5）μg/ml，透析后的中位数为 0.0（IQR：0.0-0.5，范围 0.0-5.5）μg/ml（p<0.001）。透析前后甘露糖结合凝集素和长 pentraxin 3 无显著差异（p>0.05）。在 160 例随机亚组患者中，由于血液透析，纤维胶素-2 结合、纤维胶素-3 介导的凝集素途径容量和经典途径容量显著降低。替代途径的补体容量在血液透析后增加（p=0.0101），而甘露糖结合凝集素介导的凝集素途径容量没有改变（p=0.79）。补体激活产物 C3c 增加（p<0.0001），而总 C4 和 C3 的浓度没有变化（p>0.158）。多变量 Cox 比例风险分析显示，血液透析后纤维胶素-2 增加（p=0.002）与全因死亡率增加相关。
纤维胶素-2 在血液透析后几乎从循环中耗尽。然而，血液透析后血浆纤维胶素-2 水平升高与死亡率增加独立相关。
