Abstract

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.

Keywords: Kidney Failure, Chronic - physiopathology