Elevated plasminogen activator inhibitor levels in cyclosporin-treated renal allograft recipients

Atherosclerosis and thrombosis, two major causes of morbidityand mortality in renal transplant recipients, share the sameclinical risk factors including decreased fibrinolysis and lipiddisturbances. In a crosssectional study we have determined parametersof fibrinolysis in control subjects (n=23) and stable renalallograft recipients without cyclosporin CsA (n=10) and withCsA (n=87) in their immunosuppressive treatment. In CsA-treatedpatients, tissue-type plasminogen activator was moderately increasedcompared to patients without CsA (8.4±3.3 vs 5.5±2.8ng/ml). The plasminogen activator inhibitor (PAI) activity inplasma was clearly increased in CsA-treated patients: 14.5±8.8vs 7.2±3.2 in normal controls and 8.5±2.4 AU/mlin patients without CsA. Total cholesterol and LDL cholesterollevels were higher in CsA-treated patients (256±62 and169±60 mg/dl) than in patients without CsA (209±45and 136±44 mg/dl). The two groups did not differ in HDLcholesterol, triglycerides, and lipoprotein(a). Hypercholesterolaemia,obesity, and steroid-induced diabetes could be identified asrisk factors for elevated plasma PAI activity in CsA-treatedpatients. Hypofibrinolysis induced by elevated PAI levels andincreased LDL cholesterol may contribute to the increased thrombogenicityand accelerated atherosclerosis observed in cyclosporin-treatedpatients.