Division of Nephrology, Carver College of Medicine University of Iowa, Iowa City, IA
Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Center, Aurora, CO.
J Am Heart Assoc. 2018 Jul 13;7(14):e007818. doi: 10.1161/JAHA.117.007818.
Endothelial microparticles are associated with chronic kidney disease (CKD) and complement activation. We hypothesized that the complement pathway is activated in patients with CKD via endothelial microparticles and that complement activation correlates with endothelial dysfunction in CKD.
We analyzed complement data of 30 healthy subjects, 30 patients with stage III/IV CKD, and 30 renal transplant recipients with stage III/IV CKD, evaluating the potential correlation of complement fragments with brachial artery flow-mediated dilation, Chronic Kidney Disease Epidemiology Collaboration glomerular filtration rate, and urinary albumin/creatinine ratio. Endothelial microparticles were characterized via proteomic analysis and compared between study groups. Complement fragment Ba was significantly increased in CKD and post-kidney transplant CKD. Plasma Ba levels correlated significantly with lower brachial artery flow-mediated dilation, lower Chronic Kidney Disease Epidemiology Collaboration glomerular filtration rate, and higher urinary albumin/creatinine ratio. Factor D levels were significantly higher in the plasma microparticles of patients with CKD versus healthy controls. Plasma microparticles isolated from patients with CKD and containing factor D activated the alternative pathway in vitro.
The alternative complement pathway is activated in CKD and correlates with endothelial dysfunction and markers of CKD. Future studies are needed to evaluate whether endothelial microparticles with increased factor D play a pathologic role in CKD-associated vascular disease.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT02230202.
内皮微粒与慢性肾脏病（CKD）和补体激活有关。我们假设 CKD 患者的补体途径通过内皮微粒被激活，并且补体激活与 CKD 中的内皮功能障碍相关。
我们分析了 30 名健康受试者、30 名 III/IV 期 CKD 患者和 30 名 III/IV 期 CKD 肾移植受者的补体数据，评估补体片段与肱动脉血流介导的扩张、慢性肾脏病流行病学合作肾小球滤过率和尿白蛋白/肌酐比值的潜在相关性。通过蛋白质组学分析对内皮微粒进行了特征描述，并将其与研究组进行了比较。CKD 和肾移植后 CKD 患者的补体片段 Ba 显著增加。血浆 Ba 水平与较低的肱动脉血流介导的扩张、较低的慢性肾脏病流行病学合作肾小球滤过率和较高的尿白蛋白/肌酐比值显著相关。与健康对照组相比，CKD 患者的血浆微粒中因子 D 水平显著升高。从 CKD 患者中分离出的含有因子 D 的血浆微粒在体外激活了替代途径。
替代补体途径在 CKD 中被激活，并与内皮功能障碍和 CKD 标志物相关。需要进一步研究来评估是否具有增加的因子 D 的内皮微粒在 CKD 相关血管疾病中发挥病理作用。
