Use of Defibrotide in Renal Transplantation in Man

Abstract

In transplanted patients graft rejection is the most frequent complication in the first year after surgery. Vascular lesions (necrosis, intimal proliferation, thrombosis) are signs of poor prognosis and lead to irreversible loss of renal function and graft removal in most cases. The problem of vascular rejection is still not solved and the results of therapy unsatisfactory, both because of inadequacy of diagnosis and/or inadequacy of available therapy. The role of prevention, very likely the best approach, is still sub judice. In an attempt to explore the validity of prevention, 22 transplanted patients (group A) were given a new antithrombotic agent (defibrotide) immediately after surgery, and the results were compared with those of a well-matched group of 30 patients on dipyridamole (group B). Follow-up lasted 6–19 months (mean 9.9) for group A; 5–21 months (mean 12) for group B. In group A, 8 patients (36%) had rejection episodes. Antirejection therapy was followed by recovery of renal function in all cases. In group B, 9 patients (29%) had rejection crises and graft removal was necessary in 7 instances due to severe vascular lesions. At the end of follow-up, all patients treated with defibrotide had normally functioning grafts: among the 30 patients on dipyridamole, 22 (73%) had satisfactory graft function.

Pharmacologic Intervention to Prevent Hemodialysis Vascular Access Thrombosis

“…Initially, it was shown to reduce intimal hyperplasia after thrombi were electrically induced in dogs [131]. In humans, II it has reduced the incidence of intimal hyperplasia in renal transplant grafts [132] and prevented thrombosis of subcla vian catheter use for total parenteral nutrition [133] and reversed the acute renal failure associated with endothelial injury in hemolytic uremic syndrome and thrombotic thrombocytopenic purpura [134]. More recently, cyclos porin-treated rats have been found to have an increase in PGL produced by defibrotide which was thought to confer a protective effect against cyclosporin-produced glomeru lar injury [135].…”

Effects of Defibrotide on Renal Function and Urinary Prostanoid Excretion in Ciclosporin-Treated Rats

“…Moreover, it was found to have profibrinolytic action [11] and antithrom botic activity [10]. Preliminary works suggest that it may be useful to reduce vascular lesions in experimental [12] and clinical [13] transplantation and in hemolitic-uremic syndrome [14], Therefore, theoretically its use in renal transplant patients could be useful both to reduce the danger of thrombosis and to reduce CS nephrotoxicity by increasing PGI2 synthesis. However, no data are yet available concerning the effect of the interaction of CS and DF on renal prostanoid synthesis and renal function.…”