Improved fibrinolytic capacity after withdrawal of steroid immunosuppression in renal transplant recipients.
BACKGROUND
Long-term steroid immunosuppression has been associated with the prothrombotic state observed in renal transplant (RT) patients, in whom both hypercoagulability due to an increase of von Willebrand factor/factor VIII complex, and impaired fibrinolysis due to PAI-1 excess have been demonstrated. Our aim was to investigate the effect of steroid withdrawal on fibrinolytic capacity in a group of RT patients.


METHODS
The fibrinolytic study was performed in 28 RT patients under stable immunosuppression therapy with cyclosporine, azathioprine, and methylprednisolone; only 12 of these patients could repeat the study 6 months after steroid withdrawal. Euglobulin lysis time (ELT), tissue plasminogen activator activity (t-PA:act) and antigen (t-PA:Ag), PAI-1 activity (PAI-1:act), and antigen (PAI-1:Ag) were assayed on blood samples drawn before and 20 min after the venous occlusion test (VO).


RESULTS
An hypofibrinolytic state due to a significant increase in PAI-1 levels was confirmed in RT patients receiving triple immunosuppression therapy. RT patient who stayed off steroids showed a significant shortening of ELT both before (P=0.01) and 20' after VO (P=0.005) at the 6-month control. Moreover, after steroid withdrawal, PAI-1:Ag levels decreased significantly (P=0.002) and normalized; in a similar manner PAI-1:act levels also showed a significant decrease both before (P=0.001), and after VO (P=0.0001). The prevalence of RT patients with impaired fibrinolytic capacity was as high as 83.3% during steroid treatment, and dropped to 16.7% after steroid withdrawal.


CONCLUSIONS
Our findings confirm that steroid withdrawal may normalize impaired fibrinolytic capacity in RT patients; this improvement may further contribute to reduce the thrombotic risk associated with renal transplantation.
Sartori
M T
MT
Department of Medical and Surgical Sciences, Second Chair of Internal Medicine, University of Padua Medical School, Italy.
Patrassi
G M
GM
Rigotti
P
P
Marchini
F
F
Fioretti
M
M
Spiezia
L
L
Girolami
A
A
D000328:Adult; D001379:Azathioprine / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D016572:Cyclosporine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005342:Fibrinolysis; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology*; D008297:Male; D008775:Methylprednisolone / Q000009:adverse effects*; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000097:blood
D015415:Biomarkers; D007166:Immunosuppressive Agents; D017395:Plasminogen Activator Inhibitor 1; D016572:Cyclosporine; D010959:Tissue Plasminogen Activator; D001379:Azathioprine; D008775:Methylprednisolone