Treatment of progressive membranous glomerulopathy. A randomized trial comparing cyclophosphamide and corticosteroids with corticosteroids alone. The Glomerular Disease Collaborative Network

Ann Intern Med. 1992 Mar 15;116(6):438-45. doi: 10.7326/0003-4819-116-6-438.


Objective: To determine if deterioration in renal function could be ameliorated by adding cyclophosphamide to corticosteroid therapy in patients with progressive membranous glomerulopathy.

Design: Randomized, controlled treatment trial. Patients were followed for a mean of 29.2 +/- 17.1 months.

Setting: Collaborative network of 120 university and private-practice nephrologists.

Participants: Patients with membranous glomerulopathy whose renal function deteriorated (as evidenced by doubling of the serum creatinine level, a 50% fall in the glomerular filtration rate, or a sustained serum creatinine level of greater than 2.0 mg/dL [reciprocal creatinine value, 0.5], or whose nephrotic range proteinuria persisted in association with morbid complications. Of 156 patients with biopsy-proven membranous glomerulopathy, 36 became eligible for randomization. Twenty-six of these 36 patients were randomly assigned to receive one of the two treatments.

Interventions: Pulse methylprednisolone, oral corticosteroids, and 6 months of intravenous cyclophosphamide or alternate-day corticosteroid therapy alone.

Main results: At entry, no statistical differences were found between the treatment groups in duration of renal disease, age, gender, serum creatinine level, 24-hour urine protein excretion, or biopsy stage. The groups showed no difference in mean arterial blood pressure during follow-up. Four of the 13 patients receiving corticosteroids alone and 4 of the 13 patients receiving corticosteroids plus intravenous cyclophosphamide progressed to end-stage renal disease during follow-up. Reciprocal creatinine values tested at 6-month intervals showed no statistical differences between treatment groups at any time point. The log of the 24-hour protein excretion values showed no statistical differences between treatment groups after treatment. The power to detect a substantial improvement in renal function, defined as a doubling of the reciprocal of the serum creatinine, at the 0.05 significance level was 0.92.

Conclusions: Combination therapy with intravenous cyclophosphamide and corticosteroids, when compared with corticosteroid therapy alone, does not improve renal function in patients with progressive membranous glomerulopathy.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Cyclophosphamide / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Glomerulonephritis, Membranous / complications
  • Glomerulonephritis, Membranous / drug therapy*
  • Glomerulonephritis, Membranous / mortality
  • Glucocorticoids / therapeutic use*
  • Humans
  • Hypertension / complications
  • Hypertension / physiopathology
  • Kidney Failure, Chronic / etiology
  • Kidney Function Tests
  • Male
  • Middle Aged
  • Registries
  • Statistics as Topic
  • Survival Rate


  • Glucocorticoids
  • Cyclophosphamide