Fibrinolysis in chronic renal failure, dialysis and renal transplantation.
Fibrinolysis in chronic renal failure, dialysis and renal transplantation.
复制标题
慢性肾功能衰竭、透析和肾移植中的纤维蛋白溶解。
作者：
K. Opatrný;P. Zemanová;S. Opatrná;L. Vít
纤维蛋白溶解系统最为人所知的功能是其溶解血凝块的能力。纤溶的关键酶纤溶酶是由纤溶酶原经激活剂作用转化而成，其中最重要的是组织型纤溶酶原激活剂（tPA）。低水平的tPA或过高水平的纤溶酶原激活物-I（PAI-I）引起纤维蛋白溶解减退，其与动脉粥样硬化和相关血栓性并发症的发展以及静脉和动脉血栓形成的发展有因果关系。肾功能的慢性下降导致纤溶功能减退，主要是由于tPA水平低。低纤溶存在于长期血液透析和腹膜透析治疗的患者中。血液透析程序会急剧升高血浆tPA水平，主要是由于体外回路中材料的生物不相容性。在腹膜透析中，透析液停留时间与腹腔中PAI-1水平的增加相关。纤维蛋白溶解缺陷也发生在肾移植受者中。在移植患者中，主要异常也是纤溶功能低下，然而，与其他肾脏替代治疗方法的情况不同，纤溶功能低下继发于PAI-1升高。在移植患者中PAI-1的血浆水平增加的作用是发挥类固醇和环孢霉素为基础的免疫抑制，最有可能的代谢紊乱，如胰岛素抵抗或血脂异常，和遗传因素。慢性排斥反应的动物实验显示移植物中局部纤维蛋白溶解异常，特别是PAI-1表达增加。纤维蛋白溶解缺陷可能导致慢性肾功能衰竭患者动脉粥样硬化的早期和频繁发展，导致肾移植慢性功能障碍，或导致腹膜透析患者腹膜纤维化和腹膜导管阻塞。纤溶功能减退在这些并发症的发展中的确切作用，以及调节它的潜力，需要进一步研究。
The best known function of the fibrinolytic system is its ability to dissolve blood clots. The key enzyme of fibrinolysis, plasmin, is formed by conversion from plasminogen through the action of activators, the most important of which is tissue type plasminogen activator (tPA). Low levels of tPA or excessive levels of plasminogen activator inhibitor-I (PAI-I) cause hypofibrinolysis, causally related to the development of atherosclerosis and associated thrombotic complications, as well as with the development of venous and arterial thrombosis. A chronic decrease in renal function leads to hypofibrinolysis due primarily to low levels of tPA. Hypofibrinolysis is present both in patients treated by long-term hemodialysis and by peritoneal dialysis. The hemodialysis procedure acutely raises the plasma levels of tPA, primarily as a result of the bioincompatibility of materials in the extracorporeal circuit. In peritoneal dialysis, dialysis solution dwell time is associated with an increase in PAI-I levels in the abdominal cavity. Fibrinolysis defects occur also in renal transplant recipients. In transplant patients, the main abnormality is also hypofibrinolysis which, however, unlike the situation with the other methods of renal replacement therapy, is secondary to a rise in PAI-I. A role in the increase of the plasma levels of PAI-I in transplant patients is played by steroid- and cyclosporine-based immunosuppression, most likely by metabolic disorders such as insulin resistance or dyslipoproteinemia, and by genetic factors. Animal experiments with chronic rejection have shown abnormalities in local fibrinolysis in the graft, particularly increased PAI-I expression. Fibrinolysis defects may contribute to an early and frequent development of atherosclerosis in patients with chronic renal failure, to chronic dysfunction of the renal transplant, or to peritoneal fibrosis and peritoneal catheter obstruction in patients on peritoneal dialysis. The exact role of hypofibrinolysis in the development of these complications, and the potential for modulating it, warrant further research.