Plasma fibrinolytic capacity in renal transplant recipients: effect of steroid-free immunosuppression therapy.
BACKGROUND
Cardiovascular disease is the most common cause of death among renal transplant recipients (RTRs). Impaired fibrinolytic capacity caused by an increase in plasminogen activator inhibitor type 1 (PAI-1) levels is involved in the onset of atherosclerosis and thrombotic complications. Long-term steroid treatment may induce arterial hypertension and metabolic and prothrombotic changes (including up-regulation of PAI-1 synthesis), which increase the cardiovascular risk. We evaluated plasma fibrinolytic behavior in two groups of RTRs treated with different immunosuppressive regimens.


METHODS
Twenty-seven RTRs were randomized to receive long-term (17 patients) or perioperative short-term (10 patients) steroids in addition to immunosuppression with cyclosporine A plus everolimus (Certican; Novartis, Basel, Switzerland) (7 patients) or FK506 plus mycophenolate mofetil (20 patients). In each patient, fibrinolytic capacity was studied with the 20-min venous occlusion test 1 and 6 months after transplantation. The following were assayed: euglobulin lysis time, tissue-type plasminogen activator antigen, and PAI-1 antigen and activity.


RESULTS
One month after transplantation, a severe impairment of fibrinolytic capacity, mainly caused by an increase in PAI-1 antigen and activity levels, was seen in patients with and without steroid treatment. Six months after transplantation, an improvement in fibrinolytic potential as the result of a decrease in PAI-1 levels was observed only in patients without steroid therapy. None of the steroid-treated patients demonstrated PAI-1 values correlating with body mass index, blood pressure, and metabolic parameters, thus confirming the effect of exogenous factors on PAI-1 expression. Moreover, all patients revealed a slight impairment of stimulated endothelial tissue-type plasminogen activator release, regardless of any steroid treatment, which was probably attributable to calcineurin inhibitor-induced endothelial dysfunction.


CONCLUSIONS
Our study suggests that steroid-free immunosuppression is associated with a better fibrinolytic capacity in RTRs. This finding may contribute toward reducing the risk of cardiovascular events.
Sartori
Maria T
MT
Department of Medical and Surgical Sciences, Second Chair of Internal Medicine, University of Padua Medical School, Via Ospedale Civile n. 105, 35128 Padua, Italy. mtsart@unipd.it
Rigotti
Paolo
P
Marchini
Francesco
F
Spiezia
Luca
L
Baldan
Nicola
N
Furian
Lucrezia
L
Varvarikis
Costantino
C
Girolami
Antonio
A
D000328:Adult; D001790:Blood Physiological Phenomena; D016572:Cyclosporine / Q000627:therapeutic use*; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011241:Prednisone / Q000627:therapeutic use
D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D017395:Plasminogen Activator Inhibitor 1; D016572:Cyclosporine; D011241:Prednisone; D008775:Methylprednisolone