Advertisement
American Journal of Kidney Diseases

Mycophenolate Mofetil Combined With Prednisone Versus Full-Dose Prednisone in IgA Nephropathy With Active Proliferative Lesions: A Randomized Controlled Trial

Published:February 15, 2017DOI:https://doi.org/10.1053/j.ajkd.2016.11.027

      Background

      Observational studies suggest that patients with immunoglobulin A nephropathy (IgAN) with active proliferative lesions show a good response to immunosuppressive treatment.

      Study Design

      Multicenter, prospective, randomized, controlled trial.

      Setting & Participants

      176 patients with IgAN with active proliferative lesions (cellular and fibrocellular crescents, endocapillary hypercellularity, or necrosis), proteinuria with protein excretion ≥ 1.0 g/24 h, and estimated glomerular filtration rate > 30 mL/min/1.73 m2.

      Intervention

      Mycophenolate mofetil (MMF) group: MMF, 1.5 g/d, for 6 months and prednisone, 0.4 to 0.6 mg/kg/d, for 2 months and then tapered by 20% per month for the next 4 months; prednisone group: prednisone, 0.8 to 1.0 mg/kg/d, for 2 months and then tapered by 20% per month for the next 4 months. All patients were followed up for another 6 months.

      Outcomes

      The primary end point was complete remission rate at 6 and 12 months.

      Results

      At baseline, median estimated glomerular filtration rates were 90.2 and 94.3 mL/min/1.73 m2 and mean proteinuria was protein excretion of 2.37 and 2.47 g/24 h in the MMF and prednisone groups, respectively. At 6 months, complete remission rates were 37% (32 of 86 patients) and 38% (33 of 88 patients); the between-group difference was not statistically significant (P = 0.9). At 12 months, complete remission rates were 48% (35 of 73 patients) and 53% (38 of 72 patients) in the MMF and prednisone groups, respectively; the between-group difference was not statistically significant (P = 0.6). Incidences of Cushing syndrome and newly diagnosed diabetes mellitus were lower in the MMF group than in the prednisone group.

      Limitations

      Not all participants were treated with renin-angiotensin system blockers, relatively short follow-up.

      Conclusions

      MMF plus prednisone versus full-dose prednisone did not differ in reducing proteinuria, but patients treated with the former had fewer adverse events in patients with IgAN with active proliferative lesions.

      Index Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to American Journal of Kidney Diseases
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • International Society of Nephrology
        Kidney Disease—Improving Glocal Outcomes (KDIGO) clinical practice guideline for glomerulonephritis. Chapter 10: IgA nephropathy.
        Kidney Int Suppl. 2012; 2: 209-217
        • Wyatt R.J.
        • Julian B.A.
        IgA nephropathy.
        N Engl J Med. 2013; 368: 2402-2414
        • Rauen T.
        • Eitner F.
        • Fitzner C.
        • et al.
        Intensive supportive care plus immunosuppression in IgA nephropathy.
        N Engl J Med. 2015; 373: 2225-2236
        • Harper L.
        • Ferreira M.A.
        • Howie A.J.
        • et al.
        Treatment of vasculitic IgA nephropathy.
        J Nephrol. 2000; 13: 360-366
        • Tumlin J.A.
        • Lohavichan V.
        • Hennigar R.
        Crescentic, proliferative IgA nephropathy: clinical and histological response to methylprednisolone and intravenous cyclophosphamide.
        Nephrol Dial Transplant. 2003; 18: 1321-1329
        • Tomiyoshi Y.
        • Sakemi T.
        • Ikeda Y.
        • Ohtsuka Y.
        • Nakamura M.
        • Fujisaki T.
        Cellular crescents and segmental glomerular necrosis in IgA nephropathy are indicative of the beneficial effects of corticosteroid therapy.
        Intern Med. 2001; 40: 862-866
        • Shen X.H.
        • Liang S.S.
        • Chen H.M.
        • et al.
        Reversal of active glomerular lesions after immunosuppressive therapy in patients with IgA nephropathy: a repeat-biopsy based observation.
        J Nephrol. 2015; 28: 441-449
        • Lv J.
        • Shi S.
        • Xu D.
        • et al.
        Evaluation of the Oxford classification of IgA nephropathy: a systematic review and meta-analysis.
        Am J Kidney Dis. 2013; 62: 891-899
        • Levey A.S.
        • Stevens L.A.
        • Schmid C.H.
        • et al.
        A new equation to estimate glomerular filtration rate.
        Ann Intern Med. 2009; 150: 604-612
        • Roberts I.S.
        • Cook H.T.
        • Troyanov S.
        • et al.
        The Oxford classification of IgA nephropathy: pathology definitions, correlations, and reproducibility.
        Kidney Int. 2009; 76: 546-556
        • Pozzi C.
        • Andrulli S.
        • Del Vecchio L.
        • et al.
        Corticosteroid effectiveness in IgA nephropathy: long-term results of a randomized, controlled trial.
        J Am Soc Nephrol. 2004; 15: 157-163
        • Clopper C.J.
        • Pearson E.S.
        The use of confidence or fiducial limits illustrated in the case of the binomial.
        Biometrika. 1934; 26: 404-413
        • Hotta O.
        • Furuta T.
        • Chiba S.
        • Tomioka S.
        • Taguma Y.
        Regression of IgA nephropathy: a repeat biopsy study.
        Am J Kidney Dis. 2002; 39: 493-502
        • Manno C.
        • Torres D.D.
        • Rossini M.
        • Pesce F.
        • Schena F.P.
        Randomized controlled clinical trial of corticosteroids plus ACE-inhibitors with long-term follow-up in proteinuric IgA nephropathy.
        Nephrol Dial Transplant. 2009; 24: 3694-3701
        • Pozzi C.
        • Bolasco P.
        • Fogazzi G.
        • et al.
        Corticosteroids in IgA nephropathy: a randomised controlled trial.
        Lancet. 1999; 353: 883-887
        • Appel G.B.
        • Contreras G.
        • Dooley M.A.
        • et al.
        Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis.
        J Am Soc Nephrol. 2009; 20: 1103-1112
        • Dooley M.A.
        • Jayne D.
        • Ginzler E.M.
        • et al.
        Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis.
        N Engl J Med. 2011; 365: 1886-1895
        • Sepe V.
        • Libetta C.
        • Giuliano M.G.
        • Adamo G.
        • Dal Canton A.
        Mycophenolate mofetil in primary glomerulopathies.
        Kidney Int. 2008; 73: 154-162
        • Maes B.D.
        • Oyen R.
        • Claes K.
        • et al.
        Mycophenolate mofetil in IgA nephropathy: results of a 3-year prospective placebo-controlled randomized study.
        Kidney Int. 2004; 65: 1842-1849
        • Frisch G.
        • Lin J.
        • Rosenstock J.
        • et al.
        Mycophenolate mofetil (MMF) vs placebo in patients with moderately advanced IgA nephropathy: a double-blind randomized controlled trial.
        Nephrol Dial Transplant. 2005; 20: 2139-2145
        • Tang S.
        • Leung J.C.
        • Chan L.Y.
        • et al.
        Mycophenolate mofetil alleviates persistent proteinuria in IgA nephropathy.
        Kidney Int. 2005; 68: 802-812
        • Tang S.C.
        • Tang A.W.
        • Wong S.S.
        • Leung J.C.
        • Ho Y.W.
        • Lai K.N.
        Long-term study of mycophenolate mofetil treatment in IgA nephropathy.
        Kidney Int. 2010; 77: 543-549
        • Hogg R.J.
        • Bay R.C.
        • Jennette J.C.
        • et al.
        Randomized controlled trial of mycophenolate mofetil in children, adolescents, and adults with IgA nephropathy.
        Am J Kidney Dis. 2015; 66: 783-791
        • Lv J.
        • Xu D.
        • Perkovic V.
        • et al.
        Corticosteroid therapy in IgA nephropathy.
        J Am Soc Nephrol. 2012; 23: 1108-1116
        • Roccatello D.
        • Rossi D.
        • Marletto F.
        • et al.
        Long-term effects of methylprednisolone pulses and mycophenolate mofetil in IgA nephropathy patients at risk of progression.
        J Nephrol. 2012; 25: 198-203
        • Shoji T.
        • Nakanishi I.
        • Suzuki A.
        • et al.
        Early treatment with corticosteroids ameliorates proteinuria, proliferative lesions, and mesangial phenotypic modulation in adult diffuse proliferative IgA nephropathy.
        Am J Kidney Dis. 2000; 35: 194-201