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

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.

[1]  M. Robertson,et al.  Oxidation of low density lipoproteins from patients with renal failure or renal transplants. , 1995, Kidney international.

[2]  R. Chalmers,et al.  Effect of low-dose cyclosporin on plasma lipoproteins and markers of cholestasis in patients with psoriasis. , 1995, QJM : monthly journal of the Association of Physicians.

[3]  I. Godsland,et al.  Insulin resistance, lipoproteins, body fat and hemostasis in nonobese men with angina and a normal or abnormal coronary angiogram. , 1994, Journal of the American College of Cardiology.

[4]  E. Vilella,et al.  Low-density lipoprotein metabolism in rats treated with cyclosporine. , 1993, Metabolism: clinical and experimental.

[5]  E. Tremoli,et al.  Increased synthesis of plasminogen activator inhibitor-1 by cultured human endothelial cells exposed to native and modified LDLs. An LDL receptor-independent phenomenon. , 1993, Arteriosclerosis and thrombosis : a journal of vascular biology.

[6]  M. Seed,et al.  Does cyclosporin increase lipoprotein(a) concentrations in renal transplant recipients? , 1993, The Lancet.

[7]  D. Hricik,et al.  THE EFFECTS OF STEROID WITHDRAWAL ON THE LIPOPROTEIN PROFILES OF CYCLOSPORINE‐TREATED KIDNEY AND KIDNEY‐PANCREAS TRANSPLANT RECIPIENTS , 1992, Transplantation.

[8]  J. Sambrook,et al.  Complexes of tissue-type plasminogen activator and its serpin inhibitor plasminogen-activator inhibitor type 1 are internalized by means of the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[9]  J. Simons,et al.  Lipoprotein(a) levels in chronic renal disease states, dialysis and transplantation. , 1992, Australian and New Zealand journal of medicine.

[10]  D. Raccah,et al.  Hemobiology, vascular disease, and diabetes with special reference to impaired fibrinolysis. , 1992, Metabolism: clinical and experimental.

[11]  R. Nachman Review: Stratton Lecture. Thrombosis and atherogenesis: molecular connections. , 1992, Blood.

[12]  D. Wilcken,et al.  Decreases in apolipoprotein(a) after renal transplantation: implications for lipoprotein(a) metabolism. , 1992, Clinical chemistry.

[13]  B. Lacour,et al.  Atherosclerosis and lipid disorders after renal transplantation. , 1991, Kidney international. Supplement.

[14]  L. Romics,et al.  Lp(a) lipoprotein concentration in serum of patients with heavy proteinuria of different origin. , 1989, Clinical chemistry.

[15]  M. Blombäck,et al.  PLASMINOGEN ACTIVATOR INHIBITOR IN PLASMA: RISK FACTOR FOR RECURRENT MYOCARDIAL INFARCTION , 1987, The Lancet.

[16]  P. Vague,et al.  Relationships between plasma insulin triglyceride, body mass index, and plasminogen activator inhibitor 1. , 1987, Diabete & metabolisme.

[17]  J. Fruchart,et al.  Lp(a) lipoprotein in patients with chronic renal failure treated by hemodialysis. , 1987, Clinical chemistry.

[18]  J. Chapman,et al.  Increased plasma LDL cholesterol after renal transplantation associated with cyclosporine immunosuppression. , 1987, Transplantation proceedings.

[19]  W. Kannel Lipids, diabetes, and coronary heart disease: insights from the Framingham Study. , 1985, American heart journal.

[20]  A. Sanghvi,et al.  The transport of cyclosporine in association with plasma lipoproteins in heart and liver transplant patients. , 1985, Transplantation proceedings.

[21]  T. Lerut,et al.  THROMBOEMBOLIC COMPLICATIONS AND HAEMOSTATIC CHANGES IN CYCLOSPORIN-TREATED CADAVERIC KIDNEY ALLOGRAFT RECIPIENTS , 1985, The Lancet.

[22]  D. Morel,et al.  Endothelial and Smooth Muscle Cells Alter Low Density Lipoprotein In Vitro by Free Radical Oxidation , 1984, Arteriosclerosis.

[23]  S P Azen,et al.  OBTAINING CONFIDENCE INTERVALS FOR THE RISK RATIO IN COHORT STUDIES , 1978 .

[24]  L. Mannucci,et al.  Hypertriglyceridemia and regulation of fibrinolytic activity. , 1992, Arteriosclerosis and thrombosis : a journal of vascular biology.

[25]  H. Cohen,et al.  Evidence for chronic platelet hyperaggregability and in vivo activation in cyclosporin-treated renal allograft recipients. , 1988, Thrombosis research.

[26]  A. Gotto,et al.  CORONARY ARTERY DISEASE Association of levels of lipoprotein Lp ( a ) , plasma lipids , and other lipoproteins with coronary artery disease documented by angiography , 2022 .