A controlled trial of cyclosporine in patients diagnosed with progressive membranous nephropathy (MGN) was carried out to determine whether cyclosporine (D) would be more effective than placebo (P) in reducing the rate of deterioration in renal function. Patients (N = 64) with MGN were placed on a restricted protein diet (< or = 0.9 g/kg) and followed closely for 12 months (Part 1). Patients at high risk of progression based on an absolute loss in creatinine clearance (CCr) of > or = 8 ml/min and persistent nephrotic range proteinuria (Pr) were selected and randomly assigned to either (D) (N = 9) or (P) (N = 8) for 12 months (Part 2). No differences in the two groups were noted at entry. After 12 months, the improvement in CCr slope in ml/min/month was significantly greater in the D patients (D + 2.1 vs. P + 0.5, mean difference 1.6; 95% CI 0.3 to 3.0, P < 0.02). This improvement was maintained in six of eight D (75%) over a mean follow-up period of 21 months. Daily Pr also improved with D (by month 3, D - 4.5 g/day vs. P + 0.7 g/day, P = 0.02) and was sustained in six of eight (75%) D patients. When Pr was expressed as a function of their concurrent CCr, the D versus P patients' time to halving was faster (P = 0.02) and absolute number higher (4/9 D vs 0/8 P). In the D group a trend towards worse hypertension and an increase in the number of transient rises in serum creatinine were noted.(ABSTRACT TRUNCATED AT 250 WORDS)

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