Methylprednisolone plus chlorambucil as compared with methylprednisolone alone for the treatment of idiopathic membranous nephropathy. The Italian Idiopathic Membranous Nephropathy Treatment Study Group

N Engl J Med. 1992 Aug 27;327(9):599-603. doi: 10.1056/NEJM199208273270904.


Background and methods: Treatment with methylprednisolone and chlorambucil may protect renal function and increase the chance of remission of the nephrotic syndrome in patients with idiopathic membranous nephropathy. To determine whether similar results might be obtained with methylprednisolone alone, we compared the effects of methylprednisolone and chlorambucil with those of methylprednisolone alone in 92 patients with the nephrotic syndrome caused by idiopathic membranous nephropathy. The patients were randomly assigned to receive either alternating one-month courses of methylprednisolone and then chlorambucil for a total of six months (group 1) or methylprednisolone alone for six months at the same cumulative dosage (group 2).

Results: Four of the 45 patients in group 1 (9 percent) and 1 of the 47 in group 2 (2 percent) stopped treatment because of side effects. At one, two, and three years, the percentage of patients who did not have the nephrotic syndrome was significantly higher in group 1 than in group 2. It was 58, 54, and 66 percent, respectively, in group 1, as compared with 26, 32, and 40 percent in group 2 (P = 0.002, 0.029, and 0.011). By year 4, the difference was no longer statistically significant: 62 percent of the patients in group 1 and 42 percent of those in group 2 did not have the nephrotic syndrome (P = 0.102). The patients in group 1 were in remission longer than those in group 2 (P = 0.008).

Conclusions: In patients with the nephrotic syndrome caused by idiopathic membranous nephropathy, treatment with methylprednisolone and chlorambucil for six months induces an earlier remission of the nephrotic syndrome than methylprednisolone alone, but the difference may diminish with time.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Chlorambucil / administration & dosage*
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Glomerulonephritis, Membranous / complications
  • Glomerulonephritis, Membranous / drug therapy*
  • Humans
  • Male
  • Methylprednisolone / administration & dosage*
  • Methylprednisolone / therapeutic use
  • Middle Aged
  • Nephrotic Syndrome / drug therapy
  • Nephrotic Syndrome / etiology
  • Odds Ratio
  • Remission Induction


  • Chlorambucil
  • Methylprednisolone