defibrotide and Glomerulonephritis

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.

Topics: Adult; Aged; Antibodies, Antineutrophil Cytoplasmic; Autoantibodies; Clinical Protocols; Combined Modality Therapy; Cyclophosphamide; Female; Fibrinolytic Agents; Glomerulonephritis; Granulomatosis with Polyangiitis; Humans; Immunosuppression Therapy; Kidney; Male; Methylprednisolone; Middle Aged; Plasma Exchange; Polydeoxyribonucleotides; Renal Dialysis; Treatment Outcome

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.

Topics: Adult; Clinical Trials as Topic; Female; Fibrinolytic Agents; Follow-Up Studies; Glomerulonephritis; Humans; Male; Nephrotic Syndrome; Polydeoxyribonucleotides; Proteinuria; Renal Circulation; Time Factors; Uremia