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高血压肾移植受者中的凝血酶激活纤溶抑制物

Thrombin activatable fibrinolysis inhibitor in hypertensive kidney transplant recipients.

作者信息

Malyszko J, Malyszko J S, Hryszko T, Mysliwiec M

机构信息

Department of Nephrology and Transplantology, Bialystok Medical University, ul. Zurawia 14, 15-540 Bialystok, Poland.

出版信息

Transplant Proc. 2006 Jan-Feb;38(1):105-7. doi: 10.1016/j.transproceed.2005.11.072.

Abstract

Kidney transplant recipients are prone to hypertension, dyslipidemia, and cardiovascular death. Hypertension is associated with hemostatic abnormalities. Thrombin activatable fibrinolysis inhibitor (TAFI) is a glycoprotein that links coagulation and fibrinolysis. The purpose of this study was to assess TAFI concentrations in renal transplant recipients in relation to blood pressure. Additionally, we evaluated thrombin activity (thrombin-antithrombin complex [TAT], prothrombin fragments 1+2 [F1+2]), thrombomodulin (TM), and the degree of plasmin generation (plasmin-antiplasmin complex [PAP]) using commercially available kits. The studies were performed on 86 renal allograft recipients (48 women, 38 men) at age range 26 to 73 years. The immunosuppressive regimen consisted of cyclosporine (CsA), prednisone, and azathioprine (n = 58) or mycophenolate mofetil (MMF; n = 28). All patients maintained sufficient and stable graft function, showing no clinical signs of rejection. In patients with hypertension (n = 68), we observed significantly higher concentrations of TAFI and of markers of thrombin generation (F1+2, TAT), and of thrombomodulin with significantly prolonged euglobulin clot lysis time (ECLT), which reflects overall fibrinolytic activity and lower fibrinolytic activity index (FAI). Both groups did not differ with respect to age, creatinine clearance, body mass index, time after transplantation, albumin, fibrinogen, and PAP. Diastolic blood pressure correlated significantly with TAFI concentrations, uric acid, and prednisone dose, whereas systolic blood pressure correlated with urea, uric acid, creatinine clearance, and MCV. Elevated TAFI concentrations and enhanced thrombin generation in hypertensive kidney transplant recipients may contribute to the hypofibrinolysis and progressive atherosclerosis in this population. Blood pressure was related to kidney function, maintenance prednisone dose, and TAFI concentration.

摘要

肾移植受者易患高血压、血脂异常和心血管死亡。高血压与止血异常有关。凝血酶激活的纤维蛋白溶解抑制剂(TAFI)是一种连接凝血和纤维蛋白溶解的糖蛋白。本研究的目的是评估肾移植受者中TAFI浓度与血压的关系。此外,我们使用市售试剂盒评估了凝血酶活性(凝血酶 - 抗凝血酶复合物[TAT]、凝血酶原片段1 + 2 [F1 + 2])、血栓调节蛋白(TM)以及纤溶酶生成程度(纤溶酶 - 抗纤溶酶复合物[PAP])。研究对象为86例年龄在26至73岁之间的同种异体肾移植受者(48名女性,38名男性)。免疫抑制方案包括环孢素(CsA)、泼尼松和硫唑嘌呤(n = 58)或霉酚酸酯(MMF;n = 28)。所有患者均维持足够且稳定的移植肾功能,无排斥反应的临床体征。在高血压患者(n = 68)中,我们观察到TAFI以及凝血酶生成标志物(F1 + 2、TAT)和血栓调节蛋白的浓度显著升高,优球蛋白凝块溶解时间(ECLT)显著延长,这反映了整体纤维蛋白溶解活性以及较低的纤维蛋白溶解活性指数(FAI)。两组在年龄、肌酐清除率、体重指数、移植后时间、白蛋白、纤维蛋白原和PAP方面无差异。舒张压与TAFI浓度、尿酸和泼尼松剂量显著相关,而收缩压与尿素、尿酸、肌酐清除率和平均红细胞体积相关。高血压肾移植受者中TAFI浓度升高和凝血酶生成增强可能导致该人群纤维蛋白溶解功能减退和动脉粥样硬化进展。血压与肾功能、维持性泼尼松剂量和TAFI浓度有关。

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