Persistent decreased fibrinolytic activity in cyclosporin-treated renal allograft recipients

Abstract

Cyclosporin (CS) may enhance or accelerate vascular endothelial injury. Both tissue plasminogen activator (t-PA) and its fast acting inhibitor (PAI-1) are synthesised and released by the vascular endothelium and regulate fibrinolytic activity. Parameters of plasma fibrinolytic activity were assessed serially for 1 year in 21 renal allograft recipients receiving long term immunosuppression with CS and low dose prednisolone. Fibrinolytic activity assessed by euglobulin clot lysis times and fibrin plate assays was significantly decreased from 1 month onwards (p < 0.02 and < 0.002 at 2 months and 1 year and p < 0.002 and < 0.002 at 1 month and 1 year post-transplantation respectively) compared with normal controls. In contrast, tissue plasminogen activator (t-PA) antigen levels were significantly increased, p < 0.02 and < 0.002 at 1 month and 1 year respectively. Tissue plasminogen activator inhibitor (PAI-1) activity was also significantly increased up to 6 months post-transplantation, p < 0.02 and < 0.02 at 1 and 6 months post-transplantation. Thus, CS-treated renal allograft recipients exhibited chronic prothrombotic fibrinolytic changes. The decreased fibrinolytic activity, which persisted even when trough whole blood CS levels were within the therapeutic range and plasma creatinine levels were approaching or were in the normal ranges, was probably attributable to increased levels of PAI-1 complexing to and inactivating t-PA released from the vascular endothelium.