Sartori Maria T, Rigotti Paolo, Marchini Francesco, Spiezia Luca, Baldan Nicola, Furian Lucrezia, Varvarikis Costantino, Girolami Antonio
Department of Medical and Surgical Sciences, Second Chair of Internal Medicine, University of Padua Medical School, Via Ospedale Civile n. 105, 35128 Padua, Italy.
Transplantation. 2003 Apr 15;75(7):994-8. doi: 10.1097/01.TP.0000058544.71993.E6.
Cardiovascular disease is the most common cause of death among renal transplant recipients (RTRs). Impaired fibrinolytic capacity caused by an increase in plasminogen activator inhibitor type 1 (PAI-1) levels is involved in the onset of atherosclerosis and thrombotic complications. Long-term steroid treatment may induce arterial hypertension and metabolic and prothrombotic changes (including up-regulation of PAI-1 synthesis), which increase the cardiovascular risk. We evaluated plasma fibrinolytic behavior in two groups of RTRs treated with different immunosuppressive regimens.
Twenty-seven RTRs were randomized to receive long-term (17 patients) or perioperative short-term (10 patients) steroids in addition to immunosuppression with cyclosporine A plus everolimus (Certican; Novartis, Basel, Switzerland) (7 patients) or FK506 plus mycophenolate mofetil (20 patients). In each patient, fibrinolytic capacity was studied with the 20-min venous occlusion test 1 and 6 months after transplantation. The following were assayed: euglobulin lysis time, tissue-type plasminogen activator antigen, and PAI-1 antigen and activity.
One month after transplantation, a severe impairment of fibrinolytic capacity, mainly caused by an increase in PAI-1 antigen and activity levels, was seen in patients with and without steroid treatment. Six months after transplantation, an improvement in fibrinolytic potential as the result of a decrease in PAI-1 levels was observed only in patients without steroid therapy. None of the steroid-treated patients demonstrated PAI-1 values correlating with body mass index, blood pressure, and metabolic parameters, thus confirming the effect of exogenous factors on PAI-1 expression. Moreover, all patients revealed a slight impairment of stimulated endothelial tissue-type plasminogen activator release, regardless of any steroid treatment, which was probably attributable to calcineurin inhibitor-induced endothelial dysfunction.
Our study suggests that steroid-free immunosuppression is associated with a better fibrinolytic capacity in RTRs. This finding may contribute toward reducing the risk of cardiovascular events.
心血管疾病是肾移植受者（RTRs）中最常见的死亡原因。纤溶酶原激活物抑制剂1（PAI-1）水平升高导致的纤溶能力受损与动脉粥样硬化和血栓形成并发症的发生有关。长期使用类固醇治疗可能会诱发动脉高血压以及代谢和血栓前状态改变（包括PAI-1合成上调），从而增加心血管风险。我们评估了两组接受不同免疫抑制方案治疗的RTRs的血浆纤溶行为。
27例RTRs被随机分为两组，一组长期（17例患者）或围手术期短期（10例患者）使用类固醇，同时接受环孢素A加依维莫司（Certican；瑞士巴塞尔诺华公司）免疫抑制治疗（7例患者），或FK506加霉酚酸酯免疫抑制治疗（20例患者）。在每位患者移植后1个月和6个月时，采用20分钟静脉闭塞试验研究纤溶能力。检测以下指标：优球蛋白溶解时间、组织型纤溶酶原激活物抗原、PAI-1抗原和活性。
移植后1个月，无论是否接受类固醇治疗，患者均出现纤溶能力严重受损，主要原因是PAI-1抗原和活性水平升高。移植后6个月，仅未接受类固醇治疗的患者纤溶潜力因PAI-1水平降低而有所改善。接受类固醇治疗的患者中，没有一例PAI-1值与体重指数、血压和代谢参数相关，从而证实了外源性因素对PAI-1表达的影响。此外，所有患者无论是否接受类固醇治疗，均显示出刺激的内皮组织型纤溶酶原激活物释放略有受损，这可能归因于钙调神经磷酸酶抑制剂诱导的内皮功能障碍。
我们的研究表明，无类固醇免疫抑制与RTRs更好的纤溶能力相关。这一发现可能有助于降低心血管事件的风险。
