Original Article Pilot 24 month study to compare mycophenolate mofetil and tacrolimus in the treatment of membranous lupus nephritis with nephrotic syndrome DESMOND YH YAP, 1 XUEQING YU, 2 XIANG-MEI CHEN, 3 FUMING LU, 5 NAN CHEN, 6 XUE-WANG LI, 4 COLIN SO TANG 1 and TAK MAO CHAN 1 1 Division of Nephrology, Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, 2 Department of Nephrology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 3 Department of Nephrology, 301 Hospital of the People’s Liberation Army, 4 Department of Nephrology, Peking Union Medical College Hospital, Beijing, 5 Department of Nephrology, Huashan Hospital, Fudan University and 6 Department of Nephrology, Ruiji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China KEY WORDS: lupus, membranous, mycophenolate mofetil, nephritis, tacrolimus. Correspondence: Professor Tak Mao Chan, Department of Medicine, University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong, China. Email: dtmchan@hku.hk Accepted for publication 24 January 2012. Accepted manuscript online 1 February 2012. doi:10.1111/j.1440-1797.2012.01574.x SUMMARY AT A GLANCE Optimal treatment of membranous lupus nephritis is still unknown, with a paucity of data on the efficacy of the various forms of immunosuppression and durations of treatment. Albeit a small study, this is a randomized trial comparing mycophenolate and tacrolimus, both new key players in treatment of lupus, with well-organized methodology. While the small numbers precludes making definite conclusions, the study demonstrates similar outcomes between the two drugs. ABSTRACT: Aim: This pilot study compared mycophenolate mofetil (MMF) and tacroli- mus (Tac) in the treatment of severe membranous lupus nephritis (MLN). Method: This was a 24 month prospective, randomized, open-label multi- centre exploratory study on Chinese patients with biopsy-proven pure Class V MLN with nephrotic syndrome. Patients were randomized to treatment with either MMF or Tac, both in combination with prednisolone and the efficacy and tolerability outcomes were examined. Results: Sixteen patients were included, seven in the MMF and nine in the Tac treatment arm. At 24 months the complete response, partial response and overall response rates were 57.1% vs. 11.1% (P = 0.049), 14.3% vs. 44.4% (P = 0.197) and 71.4% vs. 55.6% (P = 0.515) in the MMF and Tac groups, respectively. The two groups had similar reduction of proteinuria and lon- gitudinal profiles of serum albumin and creatinine levels. Serum creatinine remained stable in both groups, except in two patients who had a transient increase associated with high Tac blood levels. Adverse events in the MMF group included herpes zoster in one patient and reversible leucopenia in another, while in the Tac group four patients had severe infections and one developed new onset diabetes. No relapse occurred during the study period. Conclusion: Both MMF and Tac when combined with corticosteroids are effective treatment options for severe MLN. Membranous lupus nephritis (MLN) in the absence of sig- nificant endocapillary proliferation (Class V according to ISN/RPS 2003 Classification) typically presents with variable degrees of proteinuria with or without renal impairment and is associated with a relatively slower rate of renal function deterioration compared with focal (Class III) or diffuse pro- liferative lupus nephritis (Class IV) with 10 year renal sur- vival rates of 72–90%. 1–4 The optimal therapy for MLN remains obscure since it is relatively uncommon compared with Classes III or IV lupus nephritis. Depending on the severity of proteinuria, these patients have been treated with immunosuppressive regimens such as steroid alone, steroid with cytotoxic agents, calcineurine inhibitors, or inhibitor/ antagonist of the renin-angiotensin pathway. 5–10 Considerations of risk versus benefit may not justify heavy immunosuppression in patients with relatively mild pro- teinuria and stable renal function. The published data on the natural history of MLN presents a heterogeneous prognosis. This may be attributed to the inclusion of patients with variable severity and the different treatments studied. 4,11 Nephrology 17 (2012) 352–357 © 2012 The Authors Nephrology © 2012 Asian Pacific Society of Nephrology 352