Plasma fibrinolytic capacity in renal transplant recipients: Effect of steroid-free immunosuppression therapy.

Background. 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. Methods. 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. Results. 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. Conclusions. 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.