SAFETY AND TOLERABILITY OF CYCLOSPORINE-A (SANDIMMUN) IN IDIOPATHIC NEPHROTIC SYNDROME

The safety and tolerability of cyclosporin A (CyA, Sandimmun(R)) in idiopathic nephrotic syndrome were analyzed in 661 patients enrolled in 10 clinical studies. The majority had minimal-change nephropathy (MCN, 34%) or focal-segmental glomerulosclerosis (FSGS, 33%). The safety experience covered 435 patient years of CyA exposure. The initial CyA dose averaged 5 mg/kg/day in adults and 6 mg/kg/day in children, and was further titrated according to efficacy or adverse reactions. Relevant CyA-induced renal dysfunction occurred almost exclusively in patients (mostly FSGS) who had abnormal baseline renal function. Renal tolerability was better in patients who had complete remission of nephrotic syndrome than in those who did not respond to treatment. However, in the latter, the risk was still relatively low if CyA treatment was stopped after three to four months of treatment. Sixty-nine patients had a renal biopsy performed after one to three years of continous CyA therapy, and CyA-associated nephropathy, especially interstitial fibrosis, was seen in a few of these patients. Kidney biopsies may therefore be advisable in MCN patients treated successfully for one to two years and in whom further CyA therapy is indicated. Hypertension occurred in approximately 10% and was usually well controlled with conventional antihypertensive therapy. There were a few infectious complications, but the course of these was not unusual. Malignancies developed in five patients, including Hodgkin's lymphoma in two. Overall, adverse reactions resulted in CyA treatment discontinuation in 7.4% of patients, half of them because of renal dysfunction.