Department of Pharmacodynamics, Medical University of Bialystok, 2C Mickiewicza Str., 15-089, Białystok, Poland.
Department of Monitored Pharmacotherapy, Medical University of Bialystok, Białystok, Poland.
Int Urol Nephrol. 2018 Jan;50(1):127-135. doi: 10.1007/s11255-017-1729-1. Epub 2017 Oct 22.
Chronic kidney disease (CKD) is an estimated risk factor for increased mortality and morbidity due to fibrinolytic system disturbances. Progressive loss of renal function leads to retention of uremic toxins. Anthranilic acid (AA) is a tryptophan-derived uremic toxin with multidirectional properties that can affect the hemostatic system. The goal of this study was to examine the association between AA and the parameters of fibrinolysis at different stages of CKD.
Patients with CKD were divided into two groups: mild-to-moderate (n = 20) and severe-to-end-stage CKD (n = 28). Seventeen healthy volunteers served as an additional control group. Parameters of fibrinolysis, inflammation, and monocytes activation were determined by ELISA immune-enzymatic kits. AA levels were evaluated using high-performance liquid chromatography.
AA concentration and parameters of fibrinolysis: urokinase-type plasminogen activator (uPA), its soluble receptor (suPAR), tissue plasminogen activator (tPA), tissue plasminogen activator inhibitor-1 (PAI-1) and plasmin-antiplasmin complex (PAP) were significantly elevated in the CKD groups compared with the controls. The markers of inflammation, monocyte activation, and impaired kidney function were also increased in those with CKD. AA was positively correlated with the uPA/suPAR system in the early stages of CKD, whereas during severe-to-end-stage CKD, inverse relationships were observed between AA, tPA and PAI-1. Additionally, AA was an independent variable associated with tPA in patients with CKD overall and with uPA levels in the mild-to-moderate CKD group.
Obtained results suggest for the first time the association between AA and the fibrinolytic system in CKD patients. The distinct relationship between AA and individual parameters of fibrinolysis appears to be dependent on CKD stage.
慢性肾脏病（CKD）是由于纤维蛋白溶解系统紊乱导致死亡率和发病率增加的一个预估风险因素。肾功能逐渐丧失会导致尿毒症毒素潴留。邻氨基苯甲酸（AA）是一种色氨酸衍生的尿毒症毒素，具有多向性，可影响止血系统。本研究的目的是研究不同 CKD 阶段 AA 与纤溶参数之间的关系。
将 CKD 患者分为轻度至中度（n=20）和重度至终末期 CKD（n=28）两组。另外招募 17 名健康志愿者作为对照组。通过 ELISA 免疫酶试剂盒测定纤溶、炎症和单核细胞激活的参数。使用高效液相色谱法评估 AA 水平。
AA 浓度和纤溶参数：与对照组相比，CKD 组的尿激酶型纤溶酶原激活物（uPA）、其可溶性受体（suPAR）、组织型纤溶酶原激活物（tPA）、组织型纤溶酶原激活物抑制剂-1（PAI-1）和纤溶酶-抗纤溶酶复合物（PAP）的浓度明显升高。这些患者的炎症标志物、单核细胞激活和肾功能受损也增加。AA 在 CKD 的早期与 uPA/suPAR 系统呈正相关，而在重度至终末期 CKD 中，AA 与 tPA 和 PAI-1 呈负相关。此外，AA 是 CKD 患者总体中 tPA 的独立相关变量，也是轻度至中度 CKD 组中 uPA 水平的独立相关变量。
本研究首次提出了 CKD 患者中 AA 与纤溶系统之间的关联。AA 与纤溶系统各个参数之间的关系似乎取决于 CKD 阶段。
