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

Abstract

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.

• Authors: Amanda J Branten, Peggy W du Buf-Vereijken, Marc Vervloet, Jack F Wetzels
• Journal: American journal of kidney diseases : the official journal of the National Kidney Foundation (Am J Kidney Dis) Vol. 50 Issue 2 Pg. 248-56 (Aug 2007) ISSN: 1523-6838 [Electronic] United States
• PMID: 17660026 (Publication Type: Comparative Study, Controlled Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclophosphamide
• Mycophenolic Acid

Topics

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