Beneficial Effects of Conversion From Cyclosporine to Azathioprine on Fibrinolysis in Renal Transplant Recipients

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 19; no. 6; pp. 1555 - 1558
• Main Authors: van den Dorpel, Marinus A, Man't Veld, Arie J, Levi, Marcel, ten Cate, Jan Wouter, Weimar, Willem
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.06.1999; Hagerstown, MD Lippincott
• Subjects: Adult; Aged; Azathioprine - adverse effects; Biological and medical sciences; Cyclosporine - adverse effects; Drug toxicity and drugs side effects treatment; Female; Fibrinolysis - drug effects; Humans; Immunosuppressive Agents - adverse effects; Kidney Transplantation; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Plasminogen Activator Inhibitor 1 - blood; Prospective Studies; Prostaglandins - blood; Tissue Plasminogen Activator - blood; Toxicity: blood; Human; Toxicity; Transplantation; Homotransplantation; Fibrinolysis; Kidney; Chemotherapy; Treatment; Surgery; Prostanoid; Ciclosporin; Immunosuppressive agent; Azathioprine
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/01.ATV.19.6.1555

Cyclosporin A (CsA) has been implicated as one of the factors contributing to the high cardiovascular morbidity and mortality after renal transplantation. This may be mediated by either a high prevalence of conventional risk factors for atherosclerosis, such as hypertension, hypercholesterolemia, and diabetes mellitus, or by impairment of the fibrinolytic activity evoked by CsA, possibly through interference with prostanoid metabolism. We therefore assessed the impact of conversion of CsA to azathioprine immunosuppressive treatment on parameters of fibrinolytic activity and plasma concentration of the prostanoids prostaglandin E2 and thromboxane B2 in 18 stable renal transplant recipients. During CsA, mean arterial pressure and serum creatinine were significantly higher than during azathioprine (116 +/- 15 mm Hg versus 106 +/- 13 mm Hg, P=0.0003; and 147 +/- 34 [micro sign]mol/L versus 127 +/- 35 [micro sign]mol/L, P=0.002; mean +/- SD). On conversion, the plasma tissue plasminogen activator activity increased from 1.2 (1.1 to 1.7; median, 95% CI) to 1.8 (1.6 to 2.0) IU/mL (P=0.011), without a significant change of the plasminogen activator antigen concentration. This was associated with a substantial decrease in plasminogen activator inhibitor-1 activity from 10.4 (8.5 to 16.7) to 6.4 (5.6 to 9.2) IU/mL (P=0.009). Furthermore, plasma levels of prostaglandin E2 and thromboxane B2 markedly decreased (from 9.7 [7.4 to 12.9] to 4.6 [4.3 to 8.1] pg/mL, P=0.0006; and from 106.1 [91.7 to 214.2] to 70.2 [50.3 to 85.6] pg/mL, P=0.002, respectively). During CsA, but not azathioprine, plasma tissue plasminogen activator antigen and plasminogen activator inhibitor-1 levels correlated significantly with prostaglandin E2 (r=0.53, P=0.02; and r=0.60, P=0.008, respectively), and thromboxane B2 (r=0.75, P=0.0001; and r=0.77, P=0.0001, respectively) levels. In conclusion, CsA induced substantial impairment of fibrinolytic activity, which recovered after conversion to azathioprine. The impaired fibrinolysis observed during CsA treatment may be caused by modulation of eicosanoid production or metabolism in vascular endothelial cells and possibly contributes to the high incidence of cardiovascular disease after kidney transplantation. (Arterioscler Thromb Vasc Biol. 1999;19:1555-1558.)