Original Article Prospective controlled study on mycophenolate mofetil and prednisolone in the treatment of membranous nephropathy with nephrotic syndrome TAK MAO CHAN, 1 AI WU LIN, 2 SYDNEY CW TANG, 1,3 JIA QI QIAN, 2 MAN FAI LAM, 1 YIU WING HO, 3 KAI CHUNG TSE, 1 KWOK WAH CHAN, 4 KAR NENG LAI 1 and COLIN SO TANG 1 Departments of 1 Medicine and 4 Pathology, University of Hong Kong, Queen Mary Hospital, 3 Department of Medicine, United Christian Hospital, Hong Kong, and 2 Department of Medicine, Shanghai Second Medical University, Renji Hospital, Shanghai, China SUMMARY: Background: Retrospective and anecdotal data suggest that mycophenolate mofetil (MMF) might be effective when given as rescue therapy for membranous nephropathy (MN). Prospective controlled data on MMF and prednisolone as primary therapy are lacking. Methods: A prospective, randomized, controlled, open-label study was performed to investigate the efficacy and tolerability of MMF and prednisolone as primary treatment in MN with nephrotic syndrome. MMF and prednisolone given for 6 months was compared against a modified Ponticelli regimen in 20 patients, with follow up of 15 months. Results: MMF with prednisolone and the comparative immunosuppressive regimen showed similar efficacy in proteinuria reduction, despite a lower cumulative prednisolone dose in the MMF group (3.80 1 0.28 vs 9.93 1 0.25 g, P < 0.001). Remission (composite of ‘complete’ and ‘partial’) rates were 63.6% and 66.7% in the MMF group and control group, respectively (P = 1.000). Serum creatinine and creatinine clearance remained stable during follow up. Cumulative relapse rate was 23.1% at 2 years. Chlorambucil resulted in more leucopenia compared with MMF. Conclusion: Data from this pilot study indicate that more than 60% of patients with MN and nephrotic syndrome respond to combined MMF and prednisolone treatment, and suggest potential benefits of MMF as being steroid-sparing and having less adverse effects compared with other commonly used cytotoxic agents. KEY WORDS: membranous nephropathy, mycophenolate mofetil, nephrotic syndrome. Membranous nephropathy (MN) is characterized by pro- teinuria and a significant risk for progression to chronic renal failure, and heavy proteinuria predicts an unfavour- able renal prognosis. 1–3 Alternating monthly cycles of prednisolone and chlorambucil for 6 months (Ponticelli regimen) has been reported to induce remission in about 80% of patients with MN, and treated patients showed better preservation of long-term renal function compared with non-immunosuppressive management (10-year renal survival 92% vs 60%). 4 However, commonly used immuno- suppressive treatment regimens for MN, in the form of corticosteroid with chlorambucil or cyclophosphamide, 5 although effective in a significant proportion of patients, are associated with considerable adverse effects attributed to the cytotoxic agents and high-dose corticosteroid. There is, therefore, a need to explore alternative immunosuppressive regimens. Mycophenolic acid, the active metabolite of mycophe- nolate mofetil (MMF), selectively suppresses T- and B-lymphocyte proliferation, antibody formation and adhe- sion molecule glycosylation, consequent to inhibition of de novo purine nucleotide synthesis and the depletion of gua- nosine triphosphate (GTP) in lymphocytes and monocytes. 6 It is non-mutagenic and more effective than azathioprine in preventing acute renal allograft rejection. 7 We have Correspondence: Professor Tak Mao Chan, Department of Medicine, University of Hong Kong, NCB303, Queen Mary Hospital, Pokfulam, Hong Kong, China. Email: dtmchan@hkucc.hku.hk Accepted for publication 18 May 2007. © 2007 The Authors Journal compilation © 2007 Asian Pacific Society of Nephrology NEPHROLOGY 2007; 12, 576–581 doi:10.1111/j.1440-1797.2007.00822.x