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Fibrinolysis in chronic renal failure, dialysis and renal transplantation.
Ann. Transplant. 2002: 7 (1) s.34-43, il., bibliogr. 70 poz.
Hasła klasyfikacyjne GBL:
The best known function of the fibrinolytic system is its ability to dissolve blood clots. The key enzyme of fibrinolysis, plasmin, is formed by conversion from plasminogen through the action of activators, the most important of which is tissue type plasminogen activator (tPA). Low levels of tPA or excessive levels of plasminogen activator inhibitor-I (PAI-I) cause hypofibrinolysis, causally related to the development of atherosclerosis and associated thrombotic complications, as well as with the development of venous and arterial thrombosis. A chronic decrease in renal function leads to hypofibrinolysis due primary to low levels of tPA. Hypofibrinolysis is present both in patients treated by long-term hemodialysis and by peritoneal dialysis. The hemodialysis procedure acutely raises the plasma levels of tPA, primarily as a result of the bioincompatibility of materials in the extracorporeal circuit. In peritoneal dialysis, dialysis solution dwell time is associated with an increase in PAI-I levels in the abdominal cavity. Fibrinolysis defects occur also in renal transplant recipients. In transplant patients, the main abnormality is also hypofibrinolysis which, however, unlike the situation with the other methods of renal replacement therapy, is secondary to a rise in PAI-I. A role in the increase of the plasma levels of PAI-I in transplant patients is played by steroid-and cyclosporine-based immunosuppression, most likely by metabolic disorders such as insulin resistance or dyslipoproteinemia, and by genetic factors. Animal experiments ...
Freedom from rejection and stable kidney function are excellent criteria for steroid withdrawal in tacrolimus-treated kidney transplant recipients.
Ann. Transplant. 2002: 7 (3) s.28-31, il., tab., bibliogr. 5 poz.
Hasła klasyfikacyjne GBL:
dorośli 19-44 r.ż.
Objectives: This prospective, randomized, multicentre study investigated the efficacy and safety of two tacrolimus-based regimens and their potential to withdraw steroids. Methods: In total 489 patients were randomised to receive either tacrolimus and MMF (n=243) or tacrolimus and azathioprine (n=246) concomitantly with steroids in both treatment groups. The initial oral dose of tacrolimus was 0.2 mg/kg/day, MMF dose was 1 g/day, azathioprine was administered at 1-2 mg/day. Steroids were tapered from 20 mg/day to 5 mg/day. From month 3 onwards, steroids were withdrawn in patients who were free from steroid-resistant rejection and who had serum creatinine concentrations 160 ćmol/L. Study duration was 6 months. Results: Patient survival at month 6 was 98.3 p.c. (Tac/MMF/S) and 98.4 p.c. (Tac/AzaS), graft survival at 6 month was 95.0 p.c. (Tac/MMF/S) and 93.5 p.c. (Tac/Aza/S). The 6-month incidences of biopdy-proven acute rejection were 18.9 p.c. (Tac/MMF/S compared with 28.8 p.c. (Tac/Aza/S), p=0.038. The 6-month incidence of steroid-resistant acute rejection were 2.1 p.c. (Tac/MMF/S) and 4.9 p.c. (Tac/Aza/S), p=ns. At the end of month 3, steroid withdrawal was performed in 60.5 p.c. (Tac/MMF/S) and 48.8 p.c. (Tac/Aza/S) of patients, p 0.01. During months 4-6, 2.7 p.c. of patients in the Tac/MMF group had a biopsy-confirmed acute rejection compared with 0.8 p.c. of patients in the Tac/Aza group. In patients who continued to receive steroids, the incidences of biopsy-proven acute rejection during months 4-6 were 3.5 p.c. (Tac/MMF/S) and 132,8 ćmol/L (Tac/Aza/S). Conclusion: Both tacrolimus regimens are efficacious and safe. The combination of Tacrolimus and MMF achieved a lower rejection rate and permitted a higher proportion of steroid-free patients. Ther overall incidence of acute rejection was low and kidney function was good.
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