A controlled trial of cyclophosphamide in patients with membranous glomerulonephritis

Patients with membranous glomerulonephritis (MGN), impaired renal function and the nephrotic syndrome are at high risk of developing renal failure. Twenty-six such patients were studied with serum creatinine concentrations exceeding 135 microM, and 24-hour urine protein excretion of at least 3.5 g/day to determine the potential benefit of cyclophosphamide therapy. Cyclophosphamide (mean 1.5 mg/kg/day) was given to nine patients for 23 +/- 4 months. These patients were compared with 17 concurrent controls. The two groups did not differ in clinical or laboratory features at the time of biopsy or start of treatment or its equivalent. Six of the nine cyclophosphamide treated patients and 15 of the 17 controls had received prednisone therapy. The total follow-up was 49 +/- 10 months in the treated group and 50 +/- 6 months in the controls. At last observation, serum creatinine values exceeded 400 microM in eight controls (4 on dialysis) and in none of the treated patients. The mean serum creatinine level was significantly lower (P less than 0.02) in the treated group (173 +/- 24 microM) than in controls (433 +/- 71 0.02) in the treated group (173 +/- 24 microM) than in controls (433 +/- 71 microM). The mean serum albumin level and 24-hour urine protein excretion both improved significantly with treatment as compared with controls. There were four complete remissions, five partial remissions and no patient with persistent nephrotic syndrome after treatment. In the controls, there were no complete remissions, six partial remissions and 11 patients had persistent nephrotic syndrome (P less than 0.001). Thus, cyclophosphamide therapy appears to be of benefit in patients with MGN, the nephrotic syndrome and impaired renal function.