Low-Dose Mycophenolate Mofetil Therapy for Taiwanese with Refractory Glomerulonephritis-Emphasize the Effect on Membranous Nephropathy

Background: Glomerulonephritis (GN) is a major cause of end-stage renal disease in Taiwan. Mycophenolate mofetil (MMF), has demonstrated some efficacy in the treatment of glomerular diseases. However, the adequate dose was not well defined. In this study, we evaluate the efficacy of low-dose MMF therapy for refractory GN in Taiwanese. Methods: Seventeen Taiwanese with biopsy-proven GN, who had received low-dose MMF therapy (0.5-1 g/day) for at least three months because of poor response or relapsing after steroids (dependence in 10 cases and resistance in 2), cyclosporin A (CsA) and/or cytotoxic therapy (in 5), were eligibly enrolled into this retrospective study. Therapeutic outcome variables were determined by daily protein loss (DPL), serum albumin, cholesterol, serum creatinine, and creatinine clearance before and after MMF therapy. Multivariate analysis was used to identify significant predictors of DPL reduction. Results: The majority (15 of 17, 88.2%) of patients had primary GNs, including: membranous nephropathy (MN, n=7), minimal change disease (n=5), focal and segmental glomerulosclerosis (n=2), and IgA nephropathy (n=1). The median (range) dose and duration of MMF therapy in these patients were 0.75 (0.5-1.0) g/day and 14 (3.0-49.0) months. Overall, the DPL decreased by a median of 65.0% (from 4.8 to 2.3 g/day) (P=0.009), but there was no significant change in other outcome variables. Furthermore, MN patients had significant improvement in DPL (from 4.8 to 0.4 g, P=0.018), serum albumin (from 3.3 to 3.8 g/dl, P=0.042) and cholesterol (from 290 to 213 mg/dl, P=0.028) after low-dose MMF therapy. Generally, side effects of low-dose MMF were uncommon and mild. Significant predictors of DPL reduction included concomitant use of angiotensin-converting enzyme inhibitor/angiotensin Ⅱ receptor antagonist, no previous treatment of CsA/cytotoxic drugs, and MN patients. Conclusions: Low-dose MMF therapy can modestly improve DPL and preserve renal function without notable side effects in Taiwanese with refractory GN, especially in MN. This study also suggests that effective doses of MMF may be lower in MN than other GNs.