Background/Aims: Glucocorticoids and classic immunosuppressive drugs can improve disease activity in primary glomerulonephritis (GN). However, these drugs have serious toxicity and patients frequently experience inadequate response or relapse, so there is a need for alternative agents. This multicenter uncontrolled study analyzed the efficacy and safety of mycophenolate mofetil (MMF) in high-risk patients with primary GN. Methods: A total of 51 patients with biopsy-proven membranous (n = 12), membranoproliferative (n = 15), mesangioproliferative (n = 10), focal segmental glomerulosclerosis (n = 13) and minimal change disease (n = 1) received MMF with low-dose corticosteroids for 1 year. The primary outcome included the number of patients with complete/partial remission. Results: Proteinuria significantly decreased, from its median value of 4.9 g/day (IQR 2.9–8.4) to 1.28 g/day (IQR 0.5–2.9), p < 0.001. The urine protein/creatinine ratio significantly improved, from a median of 3.72 (IQR 2.13–6.48) to 0.84 (IQR 0.42–2.01), p < 0.001. The mean area under the curve for proteinuria significantly decreased, from 4.99 ± 3.46 to 2.16 ± 2.46, between the first (visits 1–2) and last (vists 4–5) treatment periods (p < 0.001). The change was similar for every type of GN, without difference between groups. eGFR slightly increased (62.1 ± 31.8 to 65.3 ± 31.8 ml/min, p = n.s.) and ESR, total proteins, albumins, total- and HDL-cholesterol parameters improved significantly. Systolic, diastolic and mean blood pressure decreased (p < 0.02 for systolic blood pressure). The age of patients was the only independent predictor of complete or partial remission. Conclusion: MMF proved to be efficient in 70% of high-risk patients with primary GN, who reached either complete or partial remission without safety concern after 12 months of treatment. Favorable effects of MMF therapy have to be confirmed in the long term and particularly after discontinuation of the drug.

Keywords:
Primary glomerulonephritis, High-risk patients, Mycophenolate mofetil
1.
Day CJ, Cockwell P, Lipkin GW, Savage COS, Howie AJ, Adu D: Mycophenolate mofetil in the treatment of resistant idiopathic nephritic syndrome. Nephrol Dial Transplant 2002;17:2011–2013.
2.
Zhao M, Chen X, Chen Y, Liu Z, Lu F, Zhang Y, Wang H: Clinical observation of mycophenolate mofetil therapy in refractory primary nephritic syndrome. Nephrology 2003;8:105–109.
3.
Mendizabal S, Zamora I, Berbel O, Sanahuja MJ, Fuentes J, Simon J: Mycophenolate mofetil in steroid/cyclosporine-dependent/resistant nephritic syndrome. Pediatr Nephrol 2005;20:914–919.
4.
Hogg RJ, Wyatt RJ, Scientific Planning Committee of the North American IgA Nephropathy Study: A randomized controlled trial of mycophenolate mofetil in patients with IgA nephropathy. BMC Nephrol 2004;5:3. www.biomedcentral.com/1471-2369/5/3 (accessed December 2, 2008).
5.
Maes BD, Oyen R, Claes K, Evenepoel P, Kuypers D, Vanwalleghem J, Van Damme B, Vanrenterghem YFC: Mycophenolate mofetil in IgA nephropathy: results of a 3-year prospective placebo-controlled randomized study. Kidney Int 2004;65:1842–1849.
6.
Frisch G, Lin J, Rosenstock J, Markowitz G, D’Agati V, Radhakrishanan J, Preddie D, Crew J, Valeri A, Appel G: 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.
7.
Tang S, Leung JK, Chan LYY, Lui YH, Tang CSO, Kan CH, HO YW, Lai KN: Mycophenolate mofetil alleviates persistent proteinuria in IgA nephropathy. Kidney Int 2005;68:802–812.
8.
Montane B, Abitbol C, Chandar J, Strauss J, Zilleruelo G: Novel therapy of focal glomerulosclerosis with mycophenolate mofetil. Pediatr Nephrol 2003;18:771–777.
9.
Gellermann J, Querfeld U: Frequently relapsing nephritic syndrome: treatment with mycophenolate mofetil. Pediatr Nephrol 2004;19:101–104.
10.
Tang S, Ho YW, Leung CY, Lai KN: Mycophenolate mofetil in the treatment of steroid-resistant primary focal segmental glomerulosclerosis. J Nephrol 2005;18:429–432.
11.
Polenakovic M, Grcevska L, Dzikova S: Mycophenolate mofetil in treatment of idiopathic stages II–IV membranous nephropathy. Nephrol Dial Transplant 2003;18:1233–1234.
12.
Jones G, Juszczak M, Kindgdon E, Harber M, Sweny P, Burns A: Treatment of idiopathic membranoproliferative glomerulonephritis with mycophenolate mofetil and steroids. Nephrol Dial Transplant 2004;19:3160–3164.
13.
Choi MJ, Eustace JA, Gimenez LF, Atta MG, Scheel PJ, Sothinathan R, Briggs WA: Mycophenolate mofetil treatment for primary glomerular diseases. Kidney Int 2002;61:1098–1114.
14.
European Medicines Agency: Clinical Safety Data Management: Definitions and Standards for Expedited Reporting. London, EMEA, 2006. www.emea.europa.eu/pdfs/human/ich/037795en.pdf (accessed December 2, 2008).
15.
Glassock RJ: Diagnosis and natural course of membranous nephropathy. Semin Nephrol 2003;23:324–332.
16.
Miller G, Zimmerman R 3rd, Radhakrishnan J, Appel GB: Use of mycophenolate mofetil in resistant membranous nephropathy. Am J Kidney Dis 2000;36:250–256.
17.
du Buf-Verejiken P, Wetzels J: Mycophenolate mofetil (MMF) versus cyclophosphamide (CP) in patients with idiopathic membranous nephropathy (iMN) and renal insufficiency (abstract). Ann Meet Am Soc Nephrol, St Louis, 2004.
18.
Bullo B, Zdrojewski Z, Rutkowski B: Mycophenolate mofetil (MMF) therapeutic approach in patients with chronic glomerulonephritis (GN). Kidney Int 2003;64:1138–1140.
19.
Cattran DC, Appel GB, Hebert L, et al: A randomized trial of cyclosporine in patients with steroid-resistant focal segmental glomerulosclerosis. North America Nephrotic Syndrome Study Group. Kidney Int 1999;56:2220–2226.
20.
Matalon A, Valeri A, Appel GB: Treatment of focal segmental glomerulosclerosis. Sem Nephrol 2000;20:309–317.
21.
Korbet SM: Treatment of primary focal segmental glomerulosclerosis. Kidney Int 2002;62:2301–2310.
22.
Cattran DC, Wang MM, Appel GB, et al: Mycophenolate mofetil in the treatment of focal segmental glomerulosclerosis. Clin Nephrol 2004;62:405–411.
23.
Segarra A, Amoedo ML, Martinez Garcia JM, Pons S, Praga M, Izquierdo Garcia E, et al: Efficacy and safety of ‘rescue therapy’ with mycophenolate mofetil in resistant primary glomerulonephritis: a multicenter study. Nephrol Dial Transplant 2007;22:1351–1360.
© 2009 S. Karger AG, Basel
2009
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.