The Effect of Mycophenolate Mofetil versus Cyclosporine as Combination Therapy with Low Dose Corticosteroids in High-risk Patients with Idiopathic Membranous Nephropathy: a Multicenter Randomized Trial

Ji Young Choi, Dong Ki Kim, Yang Wook Kim, Tae Hyun Yoo, Jung Pyo Lee, Hyun Chul Chung, Kyu Hyang Cho, Won Suk An, Duk Hyun Lee, Hee Yeon Jung, Jang Hee Cho, Chan Duck Kim, Yong Lim Kim, Sun Hee Park, Ji Young Choi, Dong Ki Kim, Yang Wook Kim, Tae Hyun Yoo, Jung Pyo Lee, Hyun Chul Chung, Kyu Hyang Cho, Won Suk An, Duk Hyun Lee, Hee Yeon Jung, Jang Hee Cho, Chan Duck Kim, Yong Lim Kim, Sun Hee Park

Abstract

Background: Appropriate immunosuppressive therapy for patients with idiopathic membranous nephropathy (MN) remains controversial. The effect of mycophenolate mofetil (MMF) versus cyclosporine (CsA) combined with low-dose corticosteroids was evaluated in patients with idiopathic MN in a multi-center randomized trial (www.ClinicalTrials.gov NCT01282073).

Methods: A total of 39 biopsy-proven idiopathic MN patients with severe proteinuria were randomly assigned to receive MMF combined with low-dose corticosteroids (MMF group) versus CsA combined with low-dose corticosteroids (CsA group), respectively, and followed up for 48 weeks. Complete or partial remission rate of proteinuria and estimated glomerular filtration rate (eGFR) at 48 weeks were compared.

Results: The level of proteinuria at baseline and at 48 weeks was 8.9 ± 5.9 and 2.1 ± 3.1 g/day, respectively, in the MMF group compared to 8.4 ± 3.5 and 3.2 ± 5.7 g/day, respectively, in the CsA group. In total, 76.1% of the MMF group and 66.7% of the CsA group achieved remission at 48 weeks (95% confidence interval, -0.18 to 0.38). There was no difference in eGFR between the two groups. Anti-phospholipase A2 receptor Ab levels at baseline decreased at 48 weeks in the complete or partial remission group (P = 0.001), but were unchanged in the no-response group. There were no significant differences between the two groups in changes in the Gastrointestinal Symptom Rating Scale and Gastrointestinal Quality of Life Index scores from baseline to 48 weeks.

Conclusion: In combination with low-dose corticosteroids, the effect of MMF may not be inferior to that of CsA in patients with idiopathic MN, with similar adverse effects including gastrointestinal symptoms. Trial registry at ClinicalTrials.gov (NCT01282073).

Keywords: Corticosteroids; Cyclosporine; Membranous Nephropathy; Mycophenolate Mofetil.

Conflict of interest statement

The authors have no potential conflicts of interest to disclose.

© 2018 The Korean Academy of Medical Sciences.

Figures

Fig. 1
Fig. 1
Flow diagram of the multi-center, randomized trial evaluating the effect of MMF vs. CsA combined with low-dose corticosteroids in patients with idiopathic membranous nephropathy. MMF = mycophenolate mofetil, CsA = cyclosporine.
Fig. 2
Fig. 2
Probability of complete or partial remission of proteinuria in MMF and CsA groups. The cumulative incidence of complete or partial remission of proteinuria at 48 weeks was 82.8% in the MMF group and 70.9% in the CsA group, which did not significantly differ between the groups (P = 0.93). MMF = mycophenolate mofetil, CsA = cyclosporine.
Fig. 3
Fig. 3
Changes in proteinuria from baseline in MMF and CsA groups. Changes in proteinuria from baseline to 12, 24, 36, and 48 weeks were comparable between the two groups. MMF = mycophenolate mofetil, CsA = cyclosporine.
Fig. 4
Fig. 4
Anti-PLA2R Ab levels. (A) Correlation between anti-PLA2R Ab levels and 24-hour urinary protein. Anti-PLA2R Ab levels from the samples in baseline and 48 weeks were strongly correlated with 24-hour urinary protein (r = 0.546, P = 0.000). (B) Anti-PLA2R Ab levels in CR or PR groups and the NR group at baseline and at 48 weeks. Horizontal lines at the bottom, middle, and top of the boxes show the 25th, 50th, and 75th percentiles, respectively, in the box plot. Anti-PLA2R Ab levels at baseline were significantly decreased at 48 weeks in the CR or PR groups (P = 0.001), but were not significantly changed in the NR group (P = 0.679). anti-PLA2R = anti-phospholipase A2 receptor, Ab = antibodies, CR = complete remission, PR = partial remission, NR = no-response. aP < 0.05 vs. baseline.

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