Clinical and Experimental Nephrology

, Volume 14, Issue 3, pp 214–221 | Cite as

Is mycophenolate mofetil superior to pulse intravenous cyclophosphamide for induction therapy of proliferative lupus nephritis in Egyptian patients?

  • Eid M. El-ShafeyEmail author
  • Said H. Abdou
  • Mohamed M. Shareef
Original Article



Recent studies have suggested that mycophenolate mofetil (MMF) may offer advantages over intravenous cyclophosphamide (IVC) for the treatment of lupus nephritis. The aim of this study was to evaluate the efficacy of MMF compared with IVC in the induction therapy of proliferative lupus nephritis.


We randomly assigned 47 patients with newly diagnosed active proliferative lupus nephritis class III or IV to open-label oral MMF 2 g/day for 6 months or intravenous cyclophosphamide 0.5–1 g/m2 monthly for 6 months in addition to corticosteroids.


In the intention-to-treat analysis, 14 of the 24 patients (58.33%) receiving MMF and 12 of the 23 patients receiving cyclophosphamide (52.17%) had remission (P = 0.48); complete remission occurred in 6 of the 24 patients (25%) and 5 of the 23 patients (21.74%), respectively (P = 0.53). Improvements in packed cell volume, the erythrocyte sedimentation rate, anti-double-stranded DNA antibodies titer (anti-dsDNA), serum complement, proteinuria, urinary activity, renal function, serum soluble interleukin-2 receptor alpha concentration and the systemic lupus activity measure score were similar in both groups. Two patients assigned to MMF and another patient assigned to IVC developed end-stage renal failure with commencement of dialysis. Adverse events were similar. Major infections occurred in two patients in each group. There was no difference in gastrointestinal side effects, but more diarrhea occurred in those receiving MMF.


In this 24-week trial, MMF or IVC combined with corticosteroids demonstrated equal efficacy in inducing remission of proliferative lupus nephritis.


Intravenous cyclophosphamide (IVC) Mycophenolate mofetil Proliferative lupus nephritis 


Conflict of interest statement

A limitation of our study is that treatment assignment was not blinded. Although this could lead to potential bias in patient recruitment and in the interpretation of results, the marked differences in the side-effect profiles of the two drugs would probably make true blinding difficult. Another limitation of our study is its short duration and the restriction to induction therapy.


  1. 1.
    Vu TV, Escalante A. A comparison of the quality of life of patients with systemic lupus erythematosus with and without end-stage renal disease. J Rheumatol. 1999;26:2595–601.PubMedGoogle Scholar
  2. 2.
    Ward MM, Pyun E, Studenski S. Mortality risks associated with specific clinical manifestations of systemic lupus erythematosus. Arch Intern Med. 1996;156:1337–44.CrossRefPubMedGoogle Scholar
  3. 3.
    Churg JSL. Lupus nephritis. In: Churg JSL, editor. Renal disease, classification and atlas of glomerular diseases. 1st ed. New York: Igaku-Shoin; 1982. p. 127–49.Google Scholar
  4. 4.
    Mitjavila F, Pac V, Moga I, et al. Clinicopathological correlations and prognostic factors in lupus nephritis. Clin Exp Rheumatol. 1997;15:625–31.PubMedGoogle Scholar
  5. 5.
    Yoo CW, Kim MK, Lee HS. Predictors of renal outcome in diffuse proliferative lupus nephropathy: data from repeat renal biopsy. Nephrol Dial Transplant. 2000;15:1604–8.CrossRefPubMedGoogle Scholar
  6. 6.
    Hurtado A, Asato C, Escudero E, et al. Clinicopathologic correlations in lupus nephritis in Lima, Peru. Nephron. 1999;83:323–30.CrossRefPubMedGoogle Scholar
  7. 7.
    Steinberg AD, Steinberg SC. Long-term preservation of renal function in patients with lupus nephritis receiving treatment that includes cyclophosphamide versus those treated with prednisone only. Arthritis Rheum. 1991;34:945–50.CrossRefPubMedGoogle Scholar
  8. 8.
    Gourley MF, Austin HA III, Scott D, et al. Methylprednisolone and cyclophosphamide, alone or in combination, in patients with lupus nephritis. A randomized, controlled trial. Ann Intern Med. 1996;125:549–57.PubMedGoogle Scholar
  9. 9.
    Boumpas DT, Austin HA III, Fessler BJ, et al. Systemic lupus erythematosus: emerging concepts. Part I. Renal, neuropsychiatric, cardiovascular, pulmonary, and hematologic disease. Ann Intern Med. 1995;122:940–50.PubMedGoogle Scholar
  10. 10.
    Halloran P, Mathew T, Tomlanovich S, et al. Mycophenolate mofetil in renal allograft recipients: A pooled efficacy analysis of three randomized, double-blind, clinical studies in prevention of rejection. The International Mycophenolate Mofetil Renal Transplant Study Groups. Transplantation. 1997;63:39–47.CrossRefPubMedGoogle Scholar
  11. 11.
    Van Bruggen MC, Walgreen B, Rijke TP, Berden JH. Attenuation of murine lupus nephritis by mycophenolate mofetil. J Am Soc Nephrol. 1998;9:1407–15.PubMedGoogle Scholar
  12. 12.
    Dooley MA, Cosio FG, Nachman PH, et al. Mycophenolate mofetil therapy in lupus nephritis: Clinical observations. J Am Soc Nephrol. 1999;10:833–9.PubMedGoogle Scholar
  13. 13.
    Briggs WA, Choi MJ, Scheel PJ Jr. Successful mycophenolate mofetil treatment of glomerular disease. Am J Kidney Dis. 1998;31:213–7.CrossRefPubMedGoogle Scholar
  14. 14.
    Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40:1725.CrossRefPubMedGoogle Scholar
  15. 15.
    Weening JJ, D’Agati VD, Schwartz MM et al. The classification of glomerulo-nephritis in systemic lupus erythematosus revisited. J Am Soc Nephrol 2004;15:241–250 [published erratum in J Am Soc Nephrol. 2004; 15:835–6.Google Scholar
  16. 16.
    Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: A new prediction equation. Ann Intern Med. 1999;130:461–70.PubMedGoogle Scholar
  17. 17.
    Liang MH, Socher SA, Larson MG, Schur PH. Reliability and validity of sex sytems for the clinical assessment of disease activity in systemic lupus erythematosus. Arthritis Rheum. 1989;32:1107–18.CrossRefPubMedGoogle Scholar
  18. 18.
    Kim MY, Buyon JP, Petri M, et al. Equivalence trials in SLE research: issues to consider. Lupus. 1999;8:620–6.CrossRefPubMedGoogle Scholar
  19. 19.
    Appel GB, Contreras G, Dooley MA, et al. Mycophenolate Mofetil versus Cyclophosphamide for Induction Treatment of Lupus Nephritis. J Am Soc Nephrol. 2009;20:1103–12.CrossRefPubMedGoogle Scholar
  20. 20.
    Chan TM, Li FK, Tang C, et al. Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis. N Engl J Med. 2000;343:1156–62.CrossRefPubMedGoogle Scholar
  21. 21.
    Gladman DD, Goldsmith CH, Urowitz MB, et al. Sensitivity to change of 3 systemic lupus erythematosus disease activity indices: International validation. J Rheumatol. 1994;21:1468–71.PubMedGoogle Scholar
  22. 22.
    Moore RA, Derry S. Systematic review and meta-analysis of randomized trials and cohort studies of mycophenolate mofetil in lupus nephritis. Arthritis Res Ther. 2006;8:R182.CrossRefPubMedGoogle Scholar
  23. 23.
    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;2:968–75.CrossRefPubMedGoogle Scholar
  24. 24.
    Zhu B, Chen N, Lin Y, Ren H, Zhang W, Wang W, et al. Mycophenolate mofetil in induction and maintenance therapy of severe lupus nephritis: A meta-analysis of randomized controlled trials. Nephrol Dial Transplant. 2007;22:1933–42.CrossRefPubMedGoogle Scholar
  25. 25.
    Barr RG, Seliger S, Appel GB, et al. Prognosis in proliferative lupus nephritis: The role of socio-economic status and race/ethnicity. Nephrol Dial Transplant. 2003;18:2039–46.CrossRefPubMedGoogle Scholar
  26. 26.
    Contreras G, Lenz O, Pardo V, et al. Outcomes in African Americans and Hispanics with lupus nephritis. Kidney Int. 2006;69:1846–51.CrossRefPubMedGoogle Scholar
  27. 27.
    Adler M, Chambers S, Edwards C, et al. An assessment of renal failure in an SLE cohort with special reference to ethnicity, over a 25-year period. Rheumatology. 2006;45:1144–7.CrossRefPubMedGoogle Scholar
  28. 28.
    Fernández M, Alarcón GS, Calvo-Alén J, LUMINA Study Group, et al. A multiethnic, multicenter cohort of patients with systemic lupus erythematosus (SLE) as a model for the study of ethnic disparities in SLE. Arthritis Rheum. 2007;57:576–84.CrossRefPubMedGoogle Scholar
  29. 29.
    Contreras G, Pardo V, Leclerq B, et al. Sequential therapies for proliferative lupus nephritis. N Engl J Med. 2004;350:971–80.CrossRefPubMedGoogle Scholar
  30. 30.
    Illei GG, Takada K, Parkin D, et al. Renal flares are common in patients with severe proliferative lupus nephritis treated with pulse immunosuppressive therapy: longterm followup of a cohort of 145 patients participating in randomized controlled studies. Arthritis Rheum. 2002;46:995–1002.CrossRefPubMedGoogle Scholar
  31. 31.
    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;16:1076–84.CrossRefPubMedGoogle Scholar

Copyright information

© Japanese Society of Nephrology 2010

Authors and Affiliations

  • Eid M. El-Shafey
    • 1
    • 4
    Email author
  • Said H. Abdou
    • 2
  • Mohamed M. Shareef
    • 3
  1. 1.Division of Nephrology, Department of Internal MedicineTanta University Hospitals, Tanta UniversityTantaEgypt
  2. 2.Department of Clinical PathologyTanta UniversityTantaEgypt
  3. 3.Department of Pathology, Faculty of MedicineTanta UniversityTantaEgypt
  4. 4.JahraKuwait

Personalised recommendations