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营养不良-炎症综合征与腹膜透析患者的内皮功能障碍有关。

Malnutrition-inflammation syndrome is associated with endothelial dysfunction in peritoneal dialysis patients.

作者信息

Aguilera Abelardo, Sánchez-Tomero José A, Bajo María A, Ruiz-Caravaca Maria L, Alvarez Vicente, del Peso Gloria, Herranz Angel, Cuesta Maria V, Castro María J, Selgas Rafael

机构信息

Servicio de Nefrologia, Hospital Universitario de la Princesa, Madrid, Spain.

出版信息

Adv Perit Dial. 2003;19:240-5.

Abstract

Endothelial dysfunction with atherosclerosis is a recognized complication of uremic patients. The hypoalbuminemia of peritoneal dialysis (PD) patients can induce a hypercoagulable and atherogenic state. In this study, we investigated the role played by malnutrition-inflammation syndrome on endothelial function markers in PD patients. We measured markers of nutrition [normalized protein catabolic rate (nPCR), albumin, prealbumin, insulin-like growth factor 1 (IGF-1), transferrin, and cholesterol], markers of endothelial damage and function [tissue-type plasminogen activator (tPA), thrombomodulin (TM), von Willebrand factor (vWF), and NO3 (representing NO)], markers of a coagulable state [fibrinogen and plasminogen activator inhibitor 1 (PAI-1)], markers of inflammation [tumor necrosis factor alpha (TNF alpha) and C-reactive protein (CRP)], and other endothelial injury factors [lipoprotein(a) [Lp(a)] and homocysteine]. We also performed an endothelial stimulation test consisting of right-arm venous occlusion (VO) for 10 minutes. The patients were divided into four groups according to their clinical atherosclerotic score (CAS). We studied 45 clinically stable PD patients. At baseline, statistically significant negative linear correlations were found between albumin and age (r = -0.54, p < 0.05), albumin and vWF post-VO (r = -0.54, p < 0.05), and albumin and TM (r = -0.36, p < 0.05), which are endothelial damage markers and prothrombotic factors. A positive linear correlation was seen between albumin and NO3 post-VO (r = 0.48, p < 0.05), indicating a high vasodilatation capacity. C-Reactive protein and TNF alpha showed a positive linear correlation (r = 0.5, p < 0.01). Similarly, TNF alpha showed a positive linear correlation with cardiovascular risk markers such as fibrinogen (r = 0.79, p < 0.01), PAI-1 (r = 0.44, p < 0.05), and homocysteine (r = 0.37, p < 0.05). Creatinine clearance showed a negative linear correlation with TM (r = -0.36, p < 0.05). Patients with albumin < 4 g/dL showed a lower tPA ratio, lower NO3, and a higher CRP, TNF alpha, and Lp(a) than did patients with albumin > 4 g/dL [tPA ratio: 2.1 +/- 1.56 (n = 29) vs. 2.6 +/- 2.3 (n = 16), p < 0.05; NO3: 47 +/- 27 micrograms/mL vs. 69 +/- 33 micrograms/mL, p < 0.05; CRP: 1.8 +/- 3 mg/dL vs. 1.1 +/- 1.6 mg/dL, p < 0.05; TNF alpha: 44.4 +/- 16 pg/mL vs. 36.6 +/- 21.4 pg/mL, p < 0.05; Lp(a): 55 +/- 39 mg/dL vs. 33 +/- 21 mg/dL, p < 0.05]. Patients with a worse CAS showed higher homocysteine levels and lower albumin values. Those relationships were maintained in both periods of the study. We found no relationships between dialysis dose and endothelial function markers. In conclusion, malnutrition-inflammation syndrome may contribute to endothelial dysfunction and, consequently, to prothrombotic and proatherogenic processes in PD patients.

摘要

尿毒症患者中,内皮功能障碍合并动脉粥样硬化是一种公认的并发症。腹膜透析(PD)患者的低白蛋白血症可诱发高凝和致动脉粥样硬化状态。在本研究中,我们调查了营养不良 - 炎症综合征在PD患者内皮功能标志物中所起的作用。我们测量了营养指标[标准化蛋白分解代谢率(nPCR)、白蛋白、前白蛋白、胰岛素样生长因子1(IGF - 1)、转铁蛋白和胆固醇]、内皮损伤和功能指标[组织型纤溶酶原激活剂(tPA)、血栓调节蛋白(TM)、血管性血友病因子(vWF)和NO3(代表NO)]、凝血状态指标[纤维蛋白原和纤溶酶原激活剂抑制剂1(PAI - 1)]、炎症指标[肿瘤坏死因子α(TNFα)和C反应蛋白(CRP)]以及其他内皮损伤因子[脂蛋白(a)[Lp(a)]和同型半胱氨酸]。我们还进行了一项内皮刺激试验,包括右臂静脉闭塞(VO)10分钟。根据临床动脉粥样硬化评分(CAS)将患者分为四组。我们研究了45例临床稳定的PD患者。在基线时,发现白蛋白与年龄之间存在统计学上显著的负线性相关性(r = -0.54,p < 0.05),白蛋白与VO后vWF之间存在负线性相关性(r = -0.54,p < 0.05),白蛋白与TM之间存在负线性相关性(r = -0.36,p < 0.05),这些都是内皮损伤标志物和促血栓形成因子。白蛋白与VO后NO3之间存在正线性相关性(r = 0.48,p < 0.05),表明血管舒张能力较高。C反应蛋白和TNFα呈正线性相关(r = 0.5,p < 0.01)。同样,TNFα与心血管风险标志物如纤维蛋白原(r = 0.79,p < 0.01)、PAI - 1(r = 0.44,p < 0.05)和同型半胱氨酸(r = 0.37,p < 0.05)呈正线性相关。肌酐清除率与TM呈负线性相关(r = -0.36,p < 0.05)。白蛋白<4 g/dL的患者与白蛋白>4 g/dL的患者相比,tPA比值更低、NO3更低,而CRP、TNFα和Lp(a)更高[tPA比值:2.1±1.56(n = 29)对2.6±2.3(n = 16),p < 0.05;NO3:47±27微克/毫升对69±33微克/毫升,p < 0.05;CRP:1.8±3毫克/分升对1.1±1.6毫克/分升,p < 0.05;TNFα:44.4±16皮克/毫升对36.6±21.4皮克/毫升,p < 0.05;Lp(a):55±39毫克/分升对33±21毫克/分升,p < 0.05]。CAS较差的患者同型半胱氨酸水平较高,白蛋白值较低。这些关系在研究的两个阶段均保持不变。我们未发现透析剂量与内皮功能标志物之间存在关联。总之,营养不良 - 炎症综合征可能导致PD患者内皮功能障碍,进而导致促血栓形成和促动脉粥样硬化过程。

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