The effect of chronic allograft rejection on plasma regulators of fibrinolysis.
Chronic renal allograft rejection is often associated with the presence of fibrin thrombi in the microcirculation. Our purpose was to evaluate the influence of chronic rejection on fibrinolytic regulators in plasma of renal allograft recipients. We evaluated the concentration and activities of tPA, uPA and PAI-I in plasma from kidney allograft recipients. We studied 64 patients who underwent kidney transplantation from cadaveric allograft donors. At the time of the study 38 patients had stable graft function for at least 6 months proceeding the study, and 26 recipients had biopsy-proven chronic rejection of the kidney transplant. Control group included 30 healthy blood donors. In kidney transplant recipients we found significantly higher plasma tPA activity (median: 0.99 IU/ml; range: 0-3.8 IU/ml) in comparison to healthy controls (median: 0.15 IU/ml; range: 0-2.8 IU/ml) (p = 0.002) as well as significantly lower plasma PAI-I activity (median: 7.06 U/ml; range: 0-33.2 U/ml) in comparison to healthy controls (median: 21.8 U/ml; range: 0-36.7 U/ml), (p = 0.0001). Among transplant recipients, PAI-I plasma activity in recipients with chronic graft rejection (median: 10.16 U/ml; range: 0-33.2 U/ml) was significantly higher than in patients with stable graft function (median: 4.83 U/ml; range: 0-22.9 U/ml), (p = 0.01). In transplant recipients with stable graft function and poorly controlled hypertension we found significantly higher PAI-I plasma activity in comparison to recipients with normal blood pressure (p = 0.006). In kidney transplant recipients there was a positive correlation between the dose of prednisone and PAI-I activity in plasma (p = 0.01) and an association between BMI value and plasma PAI-I activity (p = 0.008), as well as an association between BMI value and plasma tPA-Ant concentration (p = 0.006). Among transplant recipients, patients treated with ACE inhibitors had significantly lower uPA plasma activity than the rest of the group (p = 0.003). In recipients with stable graft function we found a correlation between CsA concentration and tPA activity (p = 0.04), as well as an association between the dose of CsA and uPA-Ant concentration in plasma (p = 0.049). In patients with chronic graft rejection we found a negative correlation between the dose of prednisone and uPA-Ant plasma level (p = 0.004). Renal allograft recipients have higher tPA and lower PAI-I activities in plasma in comparison to healthy individuals. Chronic allograft rejection, is as well as poorly controlled hypertension, seem to be associated with an increase PAI-I plasma activity. In kidney graft recipients there is a relation between the value of BMI and the activity and concentration of tPA-Ant as well as the value of BMI and the PAI-I activity in plasma. Poorly controlled hypertension is associated with an increase in PAI-I plasma activity. The results of our study suggest a stimulatory effect of CsA on tPA and PAI-I plasma activities as well as on uPA-Ant concentration, while prednisone in turn seems to enhance PAI-I activity in plasma and decrease uPA expression. In renal allograft recipients ACE inhibitors seem to reduce uPA plasma activity.
Perkowska
A
A
Transplantation Institute, Warsaw Medical University, Warsaw, Poland. agape@poczta.wp.pl
Elhasade
As
A
Durlik
M
M
Placha
G
G
Gałazka
Z
Z
Lao
M
M
Gaciong
Z
Z
D000328:Adult; D015992:Body Mass Index; D002908:Chronic Disease; D035061:Control Groups; D016572:Cyclosporine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D005342:Fibrinolysis; D005938:Glucocorticoids / Q000008:administration & dosage; D006084:Graft Rejection / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D006973:Hypertension / Q000150:complications; D007166:Immunosuppressive Agents / Q000097:blood; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011241:Prednisone / Q000008:administration & dosage; D010959:Tissue Plasminogen Activator / Q000097:blood; D014568:Urokinase-Type Plasminogen Activator / Q000097:blood
D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D017395:Plasminogen Activator Inhibitor 1; D016572:Cyclosporine; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D011241:Prednisone