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

Abstract

Atherosclerosis and thrombosis, two major causes of morbidity and mortality in renal transplant recipients, share the same clinical risk factors including decreased fibrinolysis and lipid disturbances. In a cross-sectional study we have determined parameters of fibrinolysis in control subjects (n = 23) and stable renal allograft recipients without cyclosporin (CsA) (n = 10) and with CsA (n = 87) in their immunosuppressive treatment. In CsA-treated patients, tissue-type plasminogen activator was moderately increased compared to patients without CsA (8.4+/-3.3 vs 5.5+/-2.8 ng/ml). The plasminogen activator inhibitor (PAI) activity in plasma was clearly increased in CsA-treated patients: 14.5+/-8.8 vs 7.2+/-3.2 in normal controls and 8.5+/-2.4 AU/ml in patients without CsA. Total cholesterol and LDL cholesterol levels were higher in CsA-treated patients (256+/-62 and 169+/-60 mg/dl) than in patients without CsA (209+/-45 and 136+/-44 mg/dl). The two groups did not differ in HDL cholesterol, triglycerides, and lipoprotein(a). Hypercholesterolaemia, obesity, and steroid-induced diabetes could be identified as risk factors for elevated plasma PAI activity in CsA-treated patients. Hypofibrinolysis induced by elevated PAI levels and increased LDL cholesterol may contribute to the increased thrombogenicity and accelerated atherosclerosis observed in cyclosporin-treated patients.

Beneficial effects of conversion from cyclosporine to azathioprine on fibrinolysis in renal transplant recipients

“…This finding is in agreement with data from a cross-sectional study, showing that in a group of CsA-treated renal transplant recipients PAI-1 was higher than in AZA-treated transplant recipients. 15 The magnitude of the increase of plasma PAI-1 we found during CsA is comparable to the difference in PAI-1 levels between patients with an uneventful course after myocardial infarction and patients who had reinfarction. 6 The mechanism of this CsA-associated impairment of fibrinolysis is not clear.…”

Effects of Immunosuppressive Drugs on Platelet Aggregation and Soluble P-Selectin Levels in Renal Transplant Patients

“…Hypercoagulability is thought to contribute to the development and progression of atherosclerosis [2,5] and is generally attributed to combined abnormalities in platelet and coagulation-dependent hemostasis in transplanted patients. [6,7] Changes in platelet function [8,9] and fundamental classes of coagulation components, including alterations in clotting factors, fibrinogen, and clotting inhibitors, [10] as well as fibrinolytic system abnormalities [11] may play a role in the prothrombotic state observed in renal transplant patients treated with cyclosporine.…”

Alterations in the Fibrinolytic Cascade Post-transplant: Evidence of a Bimodal Expression Pattern

“…Our analysis also found several clinical factors and medications that may be important in predicting overall fibrinolytic and thrombotic activity. Given that some of these same factors also are known to either promote or mitigate both neointimal proliferation and atheromatous CAD, it is possible that these clinical factors could also influence the formation and/or progression of Tx CAD via mechanisms involving shifts in FA (26)(27)(28)(29)(30)(31)(32)(33)(34). This study is limited by the small, single center nature of the cohort and that some time points contain missing values, which could skew the significance of the time course.…”