Pawlak Krystyna, Kowalewska Anna, Mysliwiec Michal, Pawlak Dariusz
Department of Monitored Pharmacotherapy, Medical University, Bialystok, Poland.
Am J Med Sci. 2009 Oct;338(4):293-300. doi: 10.1097/MAJ.0b013e3181aa30e6.
Cellular adhesion molecules and oxidative stress play a role in the pathogenesis of atherosclerosis in patients with chronic kidney disease (CKD). Recently, it has been postulated that the kynurenine (KYN) pathway could be involved in the pathogenesis of atherosclerosis.
We evaluated the KYN, kynurenic acid (KYNA), anthranilic acid (AA), and their relations with cellular adhesion molecules: soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), sE-selectin, sP-selectin, and Cu/Zn superoxide dismutase (Cu/Zn SOD) levels as the markers of oxidative stress in the population of 132 patients with CKD and 28 healthy controls.
Compared with the controls, 2 groups of dialyzed patients had significantly increased KYN (both P < 0.01), KYNA, AA, sICAM-1, sVCAM-1, and Cu/Zn SOD levels (all P < 0.001, respectively). KYN, AA, sICAM-1, and sVCAM-1 concentrations were significantly higher in undialyzed patients with CKD compared with healthy subjects (P < 0.001, P < 0.01, and both P < 0.05, respectively). sICAM-1 and sVCAM-1 were positively associated with KYN (P < 0.0001 and P < 0.01), KYNA (P < 0.05 and P < 0.0001), AA (P < 0.01 and P < 0.0001), and with Cu/Zn SOD (both P < 0.0001, respectively) in the whole CKD group. The positive relationship existed between sICAM-1, sVCAM-1 and age, high-sensitivity C-reactive protein, creatinine, and the duration of dialysis therapy. Multivariable analysis showed that KYN was a strong independent correlate of sICAM-1, whereas Cu/Zn SOD and platelets independently and significantly predicted sVCAM-1 in patients with CKD.
This study demonstrated that KYN is independently and significantly associated with elevated sICAM-1, whereas oxidative status and platelets independently and significantly predicted increased sVCAM-1 levels in patients with CKD.
细胞黏附分子和氧化应激在慢性肾脏病（CKD）患者动脉粥样硬化的发病机制中起作用。最近，有人推测犬尿氨酸（KYN）途径可能参与动脉粥样硬化的发病机制。
我们评估了132例CKD患者和28例健康对照人群中KYN、犬尿酸（KYNA）、邻氨基苯甲酸（AA）及其与细胞黏附分子的关系：可溶性细胞间黏附分子-1（sICAM-1）、可溶性血管细胞黏附分子-1（sVCAM-1）、sE-选择素、sP-选择素以及作为氧化应激标志物的铜/锌超氧化物歧化酶（Cu/Zn SOD）水平。
与对照组相比，两组透析患者的KYN（均P < 0.01）、KYNA、AA、sICAM-1、sVCAM-1和Cu/Zn SOD水平均显著升高（分别为P < 0.001）。未透析的CKD患者的KYN、AA、sICAM-1和sVCAM-1浓度显著高于健康受试者（分别为P < 0.001、P < 0.01和P < 0.05）。在整个CKD组中，sICAM-1和sVCAM-1与KYN（P < 0.0001和P < 0.01）、KYNA（P < 0.05和P < 0.0001）、AA（P < 0.01和P < 0.0001）以及Cu/Zn SOD（均P < 0.0001）呈正相关。sICAM-1、sVCAM-1与年龄、高敏C反应蛋白、肌酐及透析治疗时间呈正相关。多变量分析显示，KYN是sICAM-1的强独立相关因素，而Cu/Zn SOD和血小板分别独立且显著地预测了CKD患者的sVCAM-1。
本研究表明，KYN与sICAM-1升高独立且显著相关，而氧化状态和血小板分别独立且显著地预测了CKD患者sVCAM-1水平的升高。
