Mycophenolate mofetil and tacrolimus versus tacrolimus alone for the treatment of idiopathic membranous glomerulonephritis: a randomised controlled trial

Aikaterini Nikolopoulou, Marie Condon, Tabitha Turner-Stokes, H Terence Cook, Neill Duncan, Jack W Galliford, Jeremy B Levy, Liz Lightstone, Charles D Pusey, Candice Roufosse, Thomas D Cairns, Megan E Griffith, Aikaterini Nikolopoulou, Marie Condon, Tabitha Turner-Stokes, H Terence Cook, Neill Duncan, Jack W Galliford, Jeremy B Levy, Liz Lightstone, Charles D Pusey, Candice Roufosse, Thomas D Cairns, Megan E Griffith

Abstract

Background: Tacrolimus (TAC) is effective in treating membranous nephropathy (MN); however relapses are frequent after treatment cessation. We conducted a randomised controlled trial to examine whether the addition of mycophenolate mofetil (MMF) to TAC would reduce relapse rate.

Methods: Forty patients with biopsy proven idiopathic MN and nephrotic syndrome were randomly assigned to receive either TAC monotherapy (n = 20) or TAC combined with MMF (n = 20) for 12 months. When patients had been in remission for 1 year on treatment the MMF was stopped and the TAC gradually withdrawn in both groups over 6 months. Patients also received supportive treatment with angiotensin blockade, statins, diuretics and anticoagulation as needed. Primary endpoint was relapse rate following treatment withdrawal. Secondary outcomes were remission rate, time to remission and change in renal function.

Results: 16/20 (80%) of patients in the TAC group achieved remission compared to 19/20 (95%) in the TAC/MMF group (p = 0.34). The median time to remission in the TAC group was 54 weeks compared to 40 weeks in the TAC/MMF group (p = 0.46). There was no difference in the relapse rate between the groups: 8/16 (50%) patients in the TAC group relapsed compared to 8/19 (42%) in the TAC/MMF group (p = 0.7). The addition of MMF to TAC did not adversely affect the safety of the treatment.

Conclusions: Addition of MMF to TAC does not alter the relapse rate of nephrotic syndrome in patients with MN.

Trial registration: This trial is registered with EudraCTN2008-001009-41 . Trial registration date 2008-10-08.

Keywords: Membranous nephropathy; Mycophenolate mofetil; Nephrotic syndrome; Randomised controlled trial; Relapse; Tacrolimus.

Conflict of interest statement

None declared. The authors declare no competing interests. The results presented in this article have not been published previously in whole or part, except in abstract form.

Figures

Fig. 1
Fig. 1
Trial profile. In the TAC/MMF group the 2 major deviations from protocol involved one patient who declined to start the MMF and one who travelled abroad and stopped the allocated trial medication
Fig. 2
Fig. 2
Complete (CR) and partial remission (PR) in the two groups
Fig. 3
Fig. 3
Time to relapse from commencement of treatment withdrawal. Relapse events occurred within 2 years from treatment withdrawal
Fig. 4
Fig. 4
a Median mycophenolic acid (MPA) level. b Median tacrolimus levels in the two groups
Fig. 5
Fig. 5
a Serum creatinine (mg/dl, excluding patients requiring dialysis). b Glomerular filtration rate in ml/min/1.73m2(excluding patients requiring dialysis) c Serum albumin g/l d: Urinary protein creatinine ratio (mg/mmol) Note: To convert serum creatinine from mg/dl to μmol/L, multiply by 88.4; estimated glomerular filtration rate calculated by the 4 variable Modification of Diet in Renal Disease study

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