This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by van den Dorpel, M. A. Articles by Weimar, W. Search for Related Content PubMed PubMed Citation Articles by van den Dorpel, M. A. Articles by Weimar, W. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB AZATHIOPRINE CYCLOSPORIN A Medline Plus Health Information Kidney Transplantation Related Collections Cardio-renal physiology/pathophysiology Risk Factors Coagulation and fibronolysis

(Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:1555-1558.)
© 1999 American Heart Association, Inc.

Thrombosis

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

Marinus A. van den Dorpel; Arie J. Man in't Veld; Marcel Levi; Jan Wouter ten Cate; Willem Weimar

From the Department of Internal Medicine I (M.A.D., A.J.M.V., W.W.), University Hospital Rotterdam, and the Department of Internal Medicine (M.L., J.W.C.), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Correspondence to M.A. van den Dorpel, MD, PhD, Department of Internal Medicine, St. Clara Hospital Rotterdam, Olympiaweg 350, 3078 HT Rotterdam, The Netherlands.

Abstract—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 µmol/L versus 127±35 µmol/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.

Key Words: kidney transplantation • cyclosporin A • fibrinolysis • prostanoids

This article has been cited by other articles:

				N. M.M. Pires, T. W.H. Pols, M. R. de Vries, C. M. van Tiel, P. I. Bonta, M. Vos, E. K. Arkenbout, H. Pannekoek, J. W. Jukema, P. H.A. Quax, et al. Activation of Nuclear Receptor Nur77 by 6-Mercaptopurine Protects Against Neointima Formation Circulation, January 30, 2007; 115(4): 493 - 500. [Abstract] [Full Text] [PDF]

				M. A. Artz, J. M.M. Boots, G. Ligtenberg, J. I. Roodnat, M. H.L. Christiaans, P. F. Vos, H. J. Blom, F. C.G.J. Sweep, P. N.M. Demacker, and L. B. Hilbrands Improved Cardiovascular Risk Profile and Renal Function in Renal Transplant Patients after Randomized Conversion from Cyclosporine to Tacrolimus J. Am. Soc. Nephrol., July 1, 2003; 14(7): 1880 - 1888. [Abstract] [Full Text] [PDF]

				T. Hryszko, J. Malyszko, J. S. Malyszko, S. Brzosko, K. Pawlak, and M. Mysliwiec A possible role of thrombin-activatable fibrinolysis inhibitor in disturbances of fibrinolytic system in renal transplant recipients Nephrol. Dial. Transplant., August 1, 2001; 16(8): 1692 - 1696. [Abstract] [Full Text] [PDF]

				C. L. Baum Weight Gain and Cardiovascular Risk After Organ Transplantation JPEN J Parenter Enteral Nutr, May 1, 2001; 25(3): 114 - 119. [Abstract] [PDF]

				S. H. Cho, S. W. Tam, S. Demissie-Sanders, S. A. Filler, and C. K. Oh Production of Plasminogen Activator Inhibitor-1 by Human Mast Cells and Its Possible Role in Asthma J. Immunol., September 15, 2000; 165(6): 3154 - 3161. [Abstract] [Full Text] [PDF]