Mycophenolate mofetil in idiopathic membranous nephropathy: a clinical trial with comparison to a historic control group treated with cyclophosphamide

Am J Kidney Dis. 2007 Aug;50(2):248-56. doi: 10.1053/j.ajkd.2007.05.015.


Background: Cyclophosphamide can decrease proteinuria and improve renal function in patients with idiopathic membranous nephropathy, but has a high risk of side effects. We studied whether mycophenolate mofetil (MMF) could be a reasonable alternative with fewer side effects.

Study design: Clinical trial with historic controls.

Settings & participants: 32 cases and 32 controls with idiopathic membranous nephropathy and renal insufficiency at multiple centers. For comparison, we selected matched historic controls treated with cyclophosphamide.

Intervention: MMF, 1 g twice daily, for 12 months versus cyclophosphamide, 1.5 mg/kg/d, for 12 months. Both groups also received intermittent methylprednisolone and alternate-day prednisone.

Outcomes & measurements: Serum creatinine, proteinuria, and side effects during and after treatment.

Results: Median follow-up was 23 months (range, 11 to 46 months). Median serum creatinine levels were 1.8 mg/dL (159 micromol/L) in both groups at baseline and 1.4 mg/dL (124 micromol/L) in the MMF group versus 1.3 mg/dL (115 micromol/L) in the cyclophosphamide group at 12 months (P = 0.4). Proteinuria values at baseline and 12 months were protein of 8.40 and 1.41 g/d in the MMF group versus 9.19 and 1.13 g/d in the cyclophosphamide group (P = 0.5 at 12 months), respectively. Cumulative incidences of remission of proteinuria at 12 months were 66% in the MMF group versus 72% in the cyclophosphamide group (P = 0.3). Five patients (16%) in the MMF group versus none in the cyclophosphamide group had disease that did not respond to therapy (P = 0.05). Twelve patients (38%) experienced a relapse and 9 patients (31%) were re-treated in the MMF group compared with 4 (13%) and 2 patients (6%) in the cyclophosphamide group (P < 0.01 and P = 0.024, respectively). Side effects occurred in 24 patients (75%) in the MMF group and 22 patients (69%) in the cyclophosphamide group (P = 0.6).

Limitations: Nonrandomized control group, short duration of follow-up.

Conclusions: A 12-month course of MMF decreased proteinuria and improved renal function in the majority of patients, but did not appear as effective or better tolerated than cyclophosphamide. Long-term data and randomized controlled trials are needed to ascertain the efficacy of MMF in patients with idiopathic membranous nephropathy.

Trial registration: NCT00135967.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Cohort Studies
  • Cyclophosphamide / therapeutic use*
  • Female
  • Follow-Up Studies
  • Glomerulonephritis, Membranous / blood
  • Glomerulonephritis, Membranous / drug therapy*
  • Glomerulonephritis, Membranous / epidemiology
  • Humans
  • Male
  • Middle Aged
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / therapeutic use
  • Proteinuria / blood
  • Proteinuria / drug therapy
  • Proteinuria / epidemiology


  • Cyclophosphamide
  • Mycophenolic Acid

Associated data