Background: Mycophenolate (MF) is effective as induction therapy for lupus nephritis (LN) in patients with normal renal function; however, little is known about its role in patients with impaired renal failure. The purpose of this study was to evaluate the response to MF in LN and its association with baseline renal function. Methods: Data were obtained for 90 patients from 12 Spanish renal units who were receiving MF as induction therapy for LN. Patients were classified into 2 groups: group 1 (estimated glomerular filtration rate [eGFR] ≥60 ml/min/1.73 m2) and group 2 (eGFR <60 ml/min/ 1.73 m2). The primary outcome measure was the percentage of patients who achieved any response and its relationship with initial eGFR. The secondary outcome measures were the percentage of patients who achieved a complete response (CR) or partial response (PR) and the appearance of relapses during treatment and side effects. Results: At initiation of MF treatment, there were no differences in the main parameters between group 1 (n = 63; eGFR 87 ± 23 ml/min/ 1.73 m2) and group 2 (n = 27; eGFR 44 ± 12 ml/min/1.73 m2). Exposure to prednisone and MF was similar. The percentages of patients who achieved a response in groups 1 and 2 were, respectively, 69.2 and 43.8% at 6 months and 81.3 and 73.7% at 12 months. CR was more frequent in group 1, whereas PR was similar in both groups. Four patients relapsed and side effects were unremarkable. Conclusions: MF is effective and safe as induction therapy for LN, and response is even achieved in patients with baseline renal impairment.

Keywords:
Lupus nephritis, Systemic lupus erythematous, Mycophenolate, Renal failure
1.
Chen YE, Korbet SM, Katz RS, Schwartz MM, Lewis EJ: Value of a complete or partial remission in severe lupus nephritis. Clin J Am Soc Nephrol 2008;3:46–53.
2.
Illei GG, Austin HA, Crane M, Collins L, Gourley MF, Yarboro CH, Vaughan EM, Kuroiwa T, Danning CL, Steinberg AD, Klippel JH, Balow JE, Boumpas DT: Combination therapy with pulse cyclophosphamide plus pulse methylprednisolone improves long-term renal outcome without adding toxicity in patients with lupus nephritis. Ann Intern Med 2001;135:248–257.
3.
Houssiau FA, Vasconcelos C, D’Cruz D, Sebastiani GD, Garrido Ed Ede R, Danieli MG, Abramovicz D, Blockmans D, Mathieu A, Direskeneli H, Galeazzi M, Gul A, Levy Y, Petera P, Popovic R, Petrovic R, Sinico RA, Cattaneo R, Font J, Depresseux G, Cosyns JP, Cervera R: Immunosuppressive therapy in lupus nephritis: the Euro-lupus nephritis trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis Rheum 2002;46:2121–2131.
4.
Grootscholten C, Ligtenberg G, Hagen EC, van den Wall Bake AW, de Glas-Vos JW, Bijl M, Assmann KJ, Bruijn JA, Weening JJ, van Houwelingen HC, Derksen RH, Berden JH: Azathioprine/methylprednisolone versus cyclophosphamide in proliferative lupus nephritis. A randomized controlled trial. Kidney Int 2006;70:732–742.
5.
Allison AC, Eugui EM: Mycophenolate mofetil and its mechanisms of action. Immunopharmacology 2000;47:85–118.
6.
Jones RB, Walsh M, Smith KG: What is the value of mycophenolate mofetil as induction and maintenance therapy in lupus nephritis? Curr Opin Rheumatol 2009;21:256–261.
7.
Bomback AS, Appel GB: Updates on the treatment of lupus nephritis. J Am Soc Nephrol 2010;21:2028–2035.
8.
Touma Z, Gladman DD, Urowitz MB, Beyene J, Uleryk EM, Shah PS: Mycophenolate mofetil for induction treatment of lupus nephritis: a systematic review and metaanalysis. J Rheumatol 2011;38:69–78.
9.
Mohan S, Radhakrishnan J: Geographical variation in the response of lupus nephritis to mycophenolate mofetil induction therapy. Clin Nephrol 2011;75:233–241.
10.
Appel GB, Contreras G, Dooley MA, Ginzler EM, Isenberg D, Jayne D, Li L-S, Mysler E, Sanchez-Guerrero J, Solomons N, Wofsy D, the Aspreva Lupus Management Study Group: Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol 2009;20:1103–1112.
11.
Rivera F, Lopez-Gomez JM, Perez-Garcia R: Clinicopathologic correlations of renal pathology in Spain. Kidney Int 2004;66:898–904.
12.
Patel SB, Korbet SM, Lewis EJ: The prognosis of severe lupus nephritis based on the modification of diet in renal disease (MDRD) study estimated glomerular filtration rate. Lupus 2011;20:256–264.
13.
Chan TM, Tse KC, Tang CS, Mok MY, Li FK: Long-term study of mycophenolate mofetil as continuous induction and maintenance treatment for diffuse proliferative lupus nephritis. J Am Soc Nephrol 2005;16:1076–1084.
14.
El-Shafey EM, Abdou SH, Shareef MM: Is mycophenolate mofetil superior to pulse intravenous cyclophosphamide for induction therapy of proliferative lupus nephritis in egyptian patients? Clin Exp Nephrol 2010;14:214–221.
15.
Ong LM, Hooi LS, Lim TO, Goh BL, Ahmad G, Ghazalli R, Teo SM, Wong HS, Tan SY, Shaariah W, Tan CC, Morad Z: Randomized controlled trial of pulse intravenous cyclophosphamide versus mycophenolate mofetil in the induction therapy of proliferative lupus nephritis. Nephrology (Carlton) 2005;10:504–510.
16.
Ginzler EM, Dooley MA, Aranow C, Kim MY, Buyon J, Merrill JT, Petri M, Gilkeson GS, Wallace DJ, Weisman MH, Appel GB: Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. N Engl J Med 2005;353:2219–2228.
17.
Wang J, Hu W, Xie H, Zhang H, Chen H, Zeng C, Liu Z, Li L: Induction therapies for class iv lupus nephritis with non-inflammatory necrotizing vasculopathy: Mycophenolate mofetil or intravenous cyclophosphamide. Lupus 2007;16:707–712.
18.
Hu W, Liu Z, Chen H, Tang Z, Wang Q, Shen K, Li L: Mycophenolate mofetil vs cyclophosphamide therapy for patients with diffuse proliferative lupus nephritis. Chin Med J (Engl) 2002;115:705–709.
19.
Cross J, Dwomoa A, Andrews P, Burns A, Gordon C, Main J, Mathieson P, O’Donoghue D, Jayne D: Mycophenolate mofetil for remission induction in severe lupus nephritis. Nephron Clin Pract 2005;100:c92–c100.
20.
Elyan M, Ballou S: The effectiveness and safety of mycophenolate mofetil in lupus nephritis. Clin Rheumatol 2009;28:835–840.
21.
Kasitanon N, Petri M, Haas M, Magder LS, Fine DM: Mycophenolate mofetil as the primary treatment of membranous lupus nephritis with and without concurrent proliferative disease: a retrospective study of 29 cases. Lupus 2008;17:40–45.
22.
Kitiyakara C, Ophascharoensuk V, Changsirikulchai S, Ingsathit A, Tankee P, Sangpanich A, Sumethkul V: Treatment of lupus nephritis and primary glomerulonephritis with enteric-coated mycophenolate sodium. Clin Nephrol 2008;69:90–101.
23.
Lu F, Tu Y, Peng X, Wang L, Wang H, Sun Z, Zheng H, Hu Z: A prospective multicentre study of mycophenolate mofetil combined with prednisolone as induction therapy in 213 patients with active lupus nephritis. Lupus 2008;17:622–629.
24.
Weng MY, Weng CT, Liu MF: The efficacy of low-dose mycophenolate mofetil for treatment of lupus nephritis in Taiwanese patients with systemic lupus erythematosus. Clin Rheumatol 2010;29:771–775.
25.
Isenberg D, Appel GB, Contreras G, Dooley MA, Ginzler EM, Jayne D, Sanchez-Guerrero J, Wofsy D, Yu X, Solomons N: Influence of race/ethnicity on response to lupus nephritis treatment: the ALMS study. Rheumatology (Oxford) 2010;49:128–140.
26.
Frutos MA, Martín A, de Ramon E, Camps MT, Valera A, García I, Fernández-Nebro A: Ciclofosfamida intravenosa en el tratamiento de la nefritis lúpica: veinte años reduciendo dosis. Nefrologia 2007;27:12–22.
27.
Gil CM, Rivera F, Crespo A, Egea JJ, Gil MT, Olivares J: Evolución de la nefropatía lúpica grave tratada con ciclofosfamida parenteral y esteroides orales. Nefrologia 1999;19:514–521.
28.
Sisó A, Ramos-Casals M, Bove A, Brito-Zeron P, Soria N, Nardi N, Testi A, Perez-de-Lis M, Diaz-Lagares C, Darnell A, Sentis J, Coca A: Outcomes in biopsy-proven lupus nephritis: Evaluation of 190 white patients from a single center. Medicine (Baltimore) 2010;89:300–307.
29.
Walsh M, James M, Jayne D, Tonelli M, Manns BJ, Hemmelgarn BR: Mycophenolate mofetil for induction therapy of lupus nephritis: a systematic review and meta-analysis. Clin J Am Soc Nephrol 2007;2:968–975.
30.
Tang Z, Yang G, Yu C, Yu Y, Wang J, Hu W, Zeng C, Chen H, Liu Z, Li L: Effects of mycophenolate mofetil for patients with crescentic lupus nephritis. Nephrology (Carlton) 2008;13:702–707.
31.
Walsh M, Solomons N, Jayne D, Aspreva Lupus Management Study Groups: Mycophenolate mofetil in patients with lupus nephritis and poor renal function: Results from a randomised control trial. J Am Soc Nephrol 2008;19:abstr sa-po2953.
32.
Radhakrishnan J, Moutzouris DA, Ginzler EM, Solomons N, Siempos II, Appel GB: Mycophenolate mofetil and intravenous cyclophosphamide are similar as induction therapy for class V lupus nephritis. Kidney Int 2010;77:152–160.
33.
Lertdumrongluk P, Somparn P, Kittanamongkolchai W, Traitanon O, Vadcharavivad S, Avihingsanon Y: Pharmacokinetics of mycophenolic acid in severe lupus nephritis. Kidney Int 2010;78:389–395.
34.
Kamanamool N, McEvoy M, Attia J, Ingsathit A, Ngamjanyaporn P, Thakkinstian A: Efficacy and adverse events of mycophenolate mofetil versus cyclophosphamide for induction therapy of lupus nephritis: systematic review and meta-analysis. Medicine (Baltimore) 2010;89:227–235.
35.
Pisoni CN, Sanchez FJ, Karim Y, Cuadrado MJ, D’Cruz DP, Abbs IC, Khamasta MA, Hughes GR: Mycophenolate mofetil in systemic lupus erythematosus: Efficacy and tolerability in 86 patients. J Rheumatol 2005;32:1047–1052.
36.
Lee YH, Woo JH, Choi SJ, Ji JD, Song GG: Induction and maintenance therapy for lupus nephritis: a systematic review and meta-analysis. Lupus 2010;19:703–710.
© 2012 S. Karger AG, Basel
2012
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.