[Concentration of tissue plasminogen activator and its inhibitor 1 in cyclosporine A-treated children with idiopathic nephrotic syndrome]

Abstract

Patients with idiopathic nephrotic syndrome (INS) are at increased risk of thromboembolic events at every stage of the disease. We assessed the function of the coagulation cascade and fibrinolysis in stable remission of INS, in children treated with cyclosporine A.

Material: The study group consisted of 17 children (10 M, 7 F; mean age 8.5 +/- 3.2 years, range 4-18 years) with 2 month-remission of steroid-dependent INS diagnosed according to the international criteria and 20 healthy, age-matched children, and 18 children in long-term INS remission serving as controls. The children with INS relapse were treated with cyclosporine A (to maintain the drug concentration value between 80 and 150 ng/ml) and low doses of steroids, according to a standard protocol.

Methods: Fibrinolysis was assessed by measurement of tissue plasminogen activator (t-PA) and tissue plasminogen activator inhibitor (PAI-1) concentrations, whereas activation of thrombinogenesis was detected by F1 + 2 prothrombin fragment concentration. Additionally, we measured selected coagulation (concentration of thrombin-antithrombin complexes, fibrinogen concentration, prothrombin time, activated partial thromboplastin time, platelet count) and biochemical (serum albumin, cholesterol, creatinine concentration) factors.

Results: In children treated with cyclosporine A increased concentrations of t-PA and PAI-1 were found (p < 0.01). The concentration of F1 + 2 prothrombin fragments was also higher when compared to controls (p < 0.05). We found also increased total cholesterol, and lower creatinine concentration in the study group.

Conclusion: Children with remission of idiopathic nephrotic syndrome treated with cyclosporine A show increased concentration of t-PA and PAI-1 and thrombinogenesis. Despite clinical and biochemical remission they may still remain at high risk of thrombosis or endothelial injury.