Skip to main content

Advertisement

Log in

Treatment of Lupus Nephritis

  • Published:
Current Rheumatology Reports Aims and scope Submit manuscript

Abstract

The treatment of lupus nephritis has evolved over the past few decades. Standard practice is to define the first 6 months of therapy as an induction phase, during which the goal of therapy is to achieve renal remission, usually with bolus intravenous infusions of the cytotoxic cyclophosphamide or the immunosuppressant mycophenolate mofetil (MMF). Following induction, therapy is continued, with some decrease in aggressive dosing for a more prolonged period of time—typically 24 months—that is aimed at preventing renal flares and smoldering disease, which could lead to continuous deterioration of renal function. During maintenance, the usual therapeutic option is immunosuppression with MMF or azathioprine. In recent years, MMF has been increasingly replacing intravenous cyclophosphamide as an initial standard of care. The current paper reviews data on these treatment strategies and suggests a possible treatment algorithm for clinical care.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Gladman DD, Ibañez D, Urowitz MB. Systemic lupus erythematosus disease activity index 2000. J Rheum. 2002;29(2):288–91.

    PubMed  Google Scholar 

  2. Isenberg DA, Rahman A, Allen A. BILAG 2004: Development and initial validation of an updated version of the British Isles Lupus Assessment Group’s disease activity index for patients with systemic lupus erythematosus. Rheumatology. 2005;44(7):902–6.

    Article  PubMed  CAS  Google Scholar 

  3. Weening JJ, D’Agati VD, Schwartz MM, et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int. 2004;65:521–30.

    Article  PubMed  Google Scholar 

  4. Austin HA, Muenz LR, Joyce KM, et al. Diffuse proliferative lupus nephritis: identification of specific pathological features affecting renal outcome. Kidney Int. 1984;25:689–95.

    Article  PubMed  Google Scholar 

  5. Bomback AS, Appel GB. Updates on the treatment of lupus nephritis. J Am Soc Nephrol. 2010;21:2028–35.

    Article  PubMed  CAS  Google Scholar 

  6. Austin HA, Klippel JH, Balow JE, et al. Therapy of lupus nephritis: controlled trial of prednisone and cytotoxic drugs. N Engl J Med. 1986;314(10):614–9.

    Article  PubMed  Google Scholar 

  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(8):945–50.

    Article  PubMed  CAS  Google Scholar 

  8. Gourley MF, Austin HA, 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(7):549–57.

    PubMed  CAS  Google Scholar 

  9. Moroni G, Quaglini S, Maccario M, et al. “Nephritic flares” are predictors of bad long-term renal outcome in lupus nephritis. Kidney Int. 1996;50:2047–53.

    Article  PubMed  CAS  Google Scholar 

  10. El Hachmi M, Jadoul M, Lefèbvre C, et al. Relapses of lupus nephritis: incidence, risk factors, serology and impact on outcome. Lupus. 2003;12:692–6.

    Article  PubMed  Google Scholar 

  11. Houssiau FA, Vasconcelos C, D’Cruz D, et al. Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis Rheum. 2003;46(8):2121–31.

    Article  Google Scholar 

  12. Houssiau FA, Vasconcelos C, D’Cruz D, et al. Early response to immunosuppressive therapy predicts good renal outcome in lupus nephritis: lessons from long-term followup of patients in the Euro-Lupus Nephritis Trial. Arthritis Rheum. 2004;50(12):3934–40.

    Article  PubMed  Google Scholar 

  13. Contreras G, Pardo V, Leclercq B, et al. Sequential therapies for proliferative lupus nephritis. N Engl J Med. 2004;350(10):971–80.

    Article  PubMed  CAS  Google Scholar 

  14. Chan TM, Li FK, Tang CS, et al. Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis. N Engl J Med. 2000;343(16):1156–62.

    Article  PubMed  CAS  Google Scholar 

  15. Chan TM, Tse KC, Tang CS, et al. Long-term study of mycophenolate mofetil as continuous induction and maintenance treatment for diffuse proliferative lupus nephritis. J Am Soc Nephrol. 2005;16(4):1076–84.

    Article  PubMed  CAS  Google Scholar 

  16. Ginzler EM, Dooley MA, Aranow C, et al. Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. N Engl J Med. 2005;353(21):2219–28.

    Article  PubMed  CAS  Google Scholar 

  17. Zhu B, Chen N, Lin Y, 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(7):1933–42.

    Article  PubMed  CAS  Google Scholar 

  18. • Appel GB, Contreras, G, Doolery MA, et al. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol. 2009;20:1103–12. This publication describes results of the international, randomized controlled clinical trial comparing MMF with IV CYC (ALMS trial). Patients responded similarly in both groups, and MMF was not shown to be superior to IV CYC as an induction treatment. It was also shown that the rates of adverse events, serious adverse events, and infections were not significantly different between the two groups.

    Article  PubMed  CAS  Google Scholar 

  19. Allison AC, Eugui EM. Mycophenolate mofetil and its mechanisms of action. Immunopharmacology. 2000;47(2–3):85–118.

    Article  PubMed  CAS  Google Scholar 

  20. Moore RA, Derry S. Systematic review and meta-analysis of randomised trials and cohort studies of mycophenolate mofetil in lupus nephritis. Arthritis Res Ther. 2006;8(6):R182.

    Article  PubMed  Google Scholar 

  21. Isenberg D, Appel GB, Contreras G, et al. Influence of race/ethnicity on response to lupus nephritis treatment: the ALMS study. Rheumatology. 2010;49:128–40.

    Article  PubMed  Google Scholar 

  22. Furie R, Looney RJ, Rovin B, et al. Efficacy and safety of rituximab in subjects with active proliferative lupus nephritis (LN): results from the randomized, double-blind phase III LUNAR study [abstract]. Arthritis Rheum. 2009;60 Suppl 10:1149.

    Google Scholar 

  23. Lu TY, Ng KP, Cambridge G, et al. A retrospective seven-year analysis of the use of B-cell depletion therapy in systemic lupus erythematosus at University College London Hospital: the first fifty patients. Arthritis Rheum. 2009;61(4):482–7.

    Article  PubMed  Google Scholar 

  24. Efficacy and safety study of abatacept to treat lupus nephritis. Available at http://www.clinicaltrials.gov/ct2/show/NCT00430677. Accessed November 2010.

  25. Abatacept and cyclophosphamide combination therapy for lupus nephritis. Available at http://clinicaltrials.gov/ct2/show/NCT00774852. Accessed November 2010.

  26. Doria A. Treatment of lupus nephritis with enteric-coated mycophenolate sodium (EC-MPS)—MyLupus exploratory study [abstract]. Arthritis Rheum. 2010;62(10):S583.

    Google Scholar 

  27. • Ginzler EM, Appel GB, Dooley MA, et al. Aspreva Lupus Management Study (ALMS): maintenance results [abstract]. Arthritis Rheum. 2010;62(10):S871–2. As a continuation of the ALMS induction trial, MMF was compared with AZA as a maintenance regimen for LN patients who achieved response during the induction phase. MMF was found to be superior to AZA in maintaining renal remission.

    Google Scholar 

  28. • Houssiau, FA, D’Cruz D, Sangle S, et al. Azathioprine versus mycophenolate mofetil for long-term immunosuppression in lupus nephritis: results from the MAINTAIN nephritis trial. Ann Rheum Dis. 2010;69:2083–9. This study presented data comparing MMF with AZA after the ELNT induction regimen. The MMF group had fewer renal flares compared with the AZA group, but this difference was not statistically significant.

    Article  PubMed  CAS  Google Scholar 

  29. Schweitzer EJ, Yoon S, Fink J, et al. Mycophenolate mofetil reduces the risk of acute rejection less in African-American than in Caucasian kidney recipients. Kidney Int. 2006;69(10):1846–51.

    Article  Google Scholar 

  30. Aringer M, Graninger WB, Steiner G, Smolen JS. Safety and efficacy of tumor necrosis factor alpha blockade in systemic lupus erythematosus: an open-label study. Arthritis Rheum. 2004;50(10):3161–9.

    Article  PubMed  CAS  Google Scholar 

  31. Moroni G, Maccario M, Banfi G, et al. Treatment of membranous lupus nephritis. Am J Kidney Dis. 1998;31:681–6.

    Article  PubMed  CAS  Google Scholar 

  32. Lewis EJ, Lawrence LG, Lan S, et al. A controlled trial of plasma plasmapheresis therapy in severe lupus nephritis. N Engl J Med. 1992;21(326):1373–9.

    Article  Google Scholar 

  33. Grootscholten C, Ligtenberg G, Hagen EC, et al. Azathioprine/methylprednisolone versus cyclophosphamide in proliferative lupus nephritis: a randomized controlled trial. Kidney Int. 2006;70:732–42.

    Article  PubMed  CAS  Google Scholar 

Download references

Disclosure

No potential conflicts of interest relevant to this article were reported.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Anca Askanase.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shum, K., Askanase, A. Treatment of Lupus Nephritis. Curr Rheumatol Rep 13, 283–290 (2011). https://doi.org/10.1007/s11926-011-0187-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11926-011-0187-5

Keywords

Navigation