Mycophenolate Mofetil in Idiopathic Membranous Nephropathy: A Clinical Trial With Comparison to a Historic Control Group Treated With Cyclophosphamide
Received 14 January 2007; accepted 24 May 2007. published online 30 June 2007.
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 μmol/L) in both groups at baseline and 1.4 mg/dL (124 μmol/L) in the MMF group versus 1.3 mg/dL (115 μmol/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.
1Department of Nephrology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
2Department of Internal Medicine, Amphia Hospital, Breda, The Netherlands
3Department of Nephrology, VU University Medical Center, Amsterdam, The Netherlands.
Address correspondence to Jack F. Wetzels, MD, PhD, Department of Nephrology, Radboud University Nijmegen Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
ABSTRACT