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This study reports on 9 patients suffering from Wegener's granulomatosis (WG) with crescentic GN and severe systemic manifestations. On admission the mean serum creatinine was 10.9 +/- 5.1 mg/dl (4-20 mg/dl); 8 patients were oliguric and required dialysis treatment. Renal biopsy showed crescents in all cases, involving 66 to 100% of glomeruli. Patients were treated with a protocol including: a plasma exchange (PE) course; methylprednisolone; cyclophosphamide; and an antithrombotic agent (defibrotide). Clinical picture and renal function progressively improved in all patients within the first 4 weeks of treatment. After 1 month serum creatinine was 2.7 +/- 0.8 mg/dl and dialysis was no longer needed in any patient. Five relapses occurred in 3 patients 12-26 months after the onset of the disease, while they were still receiving immunosuppressive treatment. At follow-up (22 to 112 months: mean 71) all patients were alive with no clinical signs of disease activity. One patient was on regular dialysis while the others had a serum creatinine of 1.2-2.8 mg/dl (mean 1.9). Our results confirm that crescentic GN associated with WG can be successfully treated even when associated with severe clinical picture and suggest that PE can contribute to control the disease without increasing immunosuppression.

To investigate the possibility of slowing down disease progression 27 patients with primary glomerular diseases unresponsive to steroids and cytotoxic drugs were treated with Defibrotide. This drug is a single stranded DNA fraction which has profibrinolytic and deaggregating properties and can promote the generation and release of prostacyclin from vascular tissue. Before treatment all patients showed proteinuria in excess of 1 g/day and 16 had a nephrotic syndrome (59%); 10 patients had serum creatinine above 1.6 mg/dl (37%) and 6 were hypertensive. After therapy a significant decrease in daily proteinuria was observed, although the reduction exceeded 50% of pre-treatment values in only 16 patients (59%). A progressive decrease in serum creatinine occurred in patients with abnormal renal function; serial measurement of renal plasma flow showed a progressive improvement with an average increase of 6 and 12%, after 1 and 3 months of treatment, respectively. These observations confirm the view that drugs improving endothelial function and renal hemodynamics can be of value in the treatment of chronic glomerular diseases and can contribute to the maintenance of renal function.

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.

Thrombotic microangiopathy (TMA) can occur whenever pathogenetic events lead to fibrin deposition in the microcirculation. It has been suggested that intravascular coagulation is important in the development of renal as well as cerebral lesions. The mortality rate in adults varies from 50 to 70%; chronic or progressive renal failure occurs in approximately two thirds of children over 2 years of age. Poor success may be due to therapy being initiated too late or to inappropriate use of antagonistic drugs, or both. In the last 2 years we have treated 8 patients with TMA (5 with thrombotic thrombocytopenic purpura; 3 with hemolytic uremic syndrome) with defibrotide, a new antithrombotic agent extracted from mammalian lungs. At admission all patients had severe renal involvement (serum creatinine 5.3-14.9 mg/dl) and coagulation abnormalities (low platelet count; high levels of circulating fibrin degradation products). There were neurological manifestations in 6 patients. Defibrotide administration was followed in 6 patients by recovery of renal function. In all patients, defibrotide therapy induced the disappearance of neurological manifestations and normalization of coagulation abnormalities. Defibrotide caused no side effects. All patients are alive after 7-22 months of follow-up.

8 patients with thrombotic microangiopathy were treated with a new antithrombotic agent, defibrotide. This drug displays considerable fibrinolytic and antithrombotic activity, and induces generation and release of a prostacyclin-like substance from vascular tissue. At admission all patients presented severe renal involvement and coagulation abnormalities. Neurological manifestations were present in 6. Defibrotide administration was followed by recovery of renal function in 6, disappearance of neurological symptoms and coagulation abnormalities in all patients. The use of defibrotide was not associated with side effects. On the basis of the results obtained in these patients, we suggest that defibrotide might be considered as a valuable drug in the management of patients with thrombotic microangiopathy.

Eighty transplanted patients were randomized to receive either a new antithrombotic agent, defibrotide (group A), or dipyridamole (group B) in addition to immunosuppressive therapy, in order to evaluate the effectiveness of these drugs in preventing graft vascular damage. While the incidence of rejection and the occurrence of specific anti-HLA antibodies were similar in the two groups, the peak serum creatinine levels during rejection were significantly lower in patients treated with defibrotide (3.3 +/- 1.8 versus 5.6 +/- 2.4 mg/dl; P less than 0.01), 97.5 per cent of whom had a still-functioning graft after a mean follow-up period of 24 months, compared with 80.5 per cent of the patients treated with dipyridamole (P less than 0.05). Graft biopsy, carried out during rejection, showed less severe vascular lesions in patients from group A than in those from group B. Our results suggest that the prophylactic administration of defibrotide may play a role in improving the long-term results of renal transplantation.