Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Update on the management of lupus nephritis: let the treatment fit the patient

Nature Clinical Practice Rheumatology volume 4, pages 464–472 (2008)Cite this article

Abstract

The introduction of new therapeutic modalities, such as biologic agents, for the treatment of lupus nephritis has re-energized research into this disorder, enabling investigators to formulate evidence-based recommendations. Thus, it is now widely accepted that the management of lupus nephritis involves a period of intensive induction therapy, followed by a longer period of less-intensive maintenance therapy. Risk stratification, based on histologic, demographic, clinical and laboratory characteristics, allows the identification of patients at high risk of renal dysfunction, for whom aggressive therapy is likely to be the most beneficial. New studies and meta-analyses comparing mycophenolate mofetil with cyclophosphamide have confirmed the efficacy of the former for induction and maintenance therapy—particularly induction therapy, owing to its favorable toxicity profile; however, claims of efficacy superior to that of cyclophosphamide require additional documentation. Nonetheless, an increasing number of physicians use mycophenolate mofetil as induction therapy for most cases of proliferative lupus nephritis, while reserving cyclophosphamide for the most severe cases. No evidence yet indicates that mycophenolate mofetil is better than azathioprine for the maintenance of remission. For patients who relapse or who are unable to be treated with these agents, rituximab seems to offer some benefit with an acceptable toxicity profile. This article summarizes the advances in the management of lupus nephritis since our 2005 Review.

Key Points

  • The treatment of lupus nephritis involves a period of intensive induction therapy, followed by a longer period of less-intensive maintenance therapy

  • Combinations of intravenous cyclophosphamide and methylprednisolone are effective for the induction and maintenance of remission in patients with severe lupus nephritis

  • Mycophenolate mofetil is an acceptable option for the induction of remission in moderately severe lupus nephritis

  • Mycophenolate mofetil or azathioprine could also be used as a maintenance therapy following cyclophosphamide induction therapy

  • In addition to immunosuppressive therapy, aggressive treatment of hypertension and hyperlipidemia is essential

  • For patients with established chronic kidney disease (estimated glomerular filtration rate <60 ml/min or stable proteinuria more than 0.5 g per day), renoprotective therapy with angiotensin-converting-enzyme inhibitors and/or angiotensin-receptor blockers is recommended

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Suggested algorithm for the treatment of lupus nephritis.

Similar content being viewed by others

References

  1. Boumpas DT et al. (1992) Controlled trial of pulse methylprednisolone versus two regimens of pulse cyclophosphamide in severe lupus nephritis. Lancet 340: 741–745

    Article  CAS  Google Scholar 

  2. Gourley MF et al. (1996) Methylprednisolone and cyclophosphamide, alone or in combination, in patients with lupus nephritis. A randomized, controlled trial. Ann Intern Med 125: 549–557

    Article  CAS  Google Scholar 

  3. Illei GG et al. (2001) Combination therapy with pulse cyclophosphamide plus pulse methylprednisolone improves long-term renal outcome without adding toxicity in patients with lupus nephritis. Ann Intern Med 135: 248–257

    Article  CAS  Google Scholar 

  4. Boumpas DT et al. (1993) Risk for sustained amenorrhea in patients with systemic lupus erythematosus receiving intermittent pulse cyclophosphamide therapy. Ann Intern Med 119: 366–369

    Article  CAS  Google Scholar 

  5. Houssiau FA et al. (2004) 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 50: 3934–3940

    Article  Google Scholar 

  6. Boumpas DT et al. (2005) Optimum therapeutic approaches for lupus nephritis: what therapy and for whom? Nat Clin Pract Rheumatol 1: 22–30

    Article  CAS  Google Scholar 

  7. Grootscholten C et al. (2006) Azathioprine/methylprednisolone versus cyclophosphamide in proliferative lupus nephritis. A randomized controlled trial. Kidney Int 70: 732–742

    Article  CAS  Google Scholar 

  8. Grootscholten C et al. (2007) Treatment with cyclophosphamide delays the progression of chronic lesions more effectively than does treatment with azathioprine plus methylprednisolone in patients with proliferative lupus nephritis. Arthritis Rheum 56: 924–937

    Article  CAS  Google Scholar 

  9. Mok CC et al. (2006) Long-term outcome of diffuse proliferative lupus glomerulonephritis treated with cyclophosphamide. Am J Med 119: e25–e33

    Article  Google Scholar 

  10. Moore RA and Derry S (2006) Systematic review and meta-analysis of randomised trials and cohort studies of mycophenolate mofetil in lupus nephritis. Arthritis Res Ther 8: 1–10

    Article  Google Scholar 

  11. Walsh M et al. (2007) Mycophenolate mofetil for induction therapy of lupus nephritis: a systematic review and meta-analysis. Clin J Am Soc Nephrol 5: 968–975

    Article  Google Scholar 

  12. Zhu B et al. (2007) Mycophenolate mofetil in induction and maintenance therapy of severe lupus nephritis: a meta-analysis of randomized controlled trials. Nephrol Dial Transplant 22: 1933–1942

    Article  CAS  Google Scholar 

  13. A study of CellCept (mycophenolate mofetil) in management of patients with lupus nephritis. [http://clinicaltrials.gov/ct/show/NCT00121082] (accessed 17 July 2008)

  14. Ginzler E. et al. (2007) Mycophenolate mofetil and intravenous cyclophosphamide in the Aspreva Lupus Management Study (ALMS): efficacy by racial group. Presented at the American College of Rheumatology Annual Meeting, 2007, Boston, MA [www.rheumatology.org]

  15. Moroni G et al. (1996) “Nephritic flares” are predictors of bad long-term renal outcome in lupus nephritis. Kidney Int 50: 2047–2053

    Article  CAS  Google Scholar 

  16. Illei GG et al. (2002) Renal flares are common in patients with severe proliferative lupus nephritis treated with pulse immunosuppressive therapy: long-term followup of a cohort of 145 patients participating in randomized controlled studies. Arthritis Rheum 46: 995–1002

    Article  CAS  Google Scholar 

  17. Chan TM et al. (2005) Long-term outcome of patients with diffuse proliferative lupus nephritis treated with prednisolone and oral cyclophosphamide followed by azathioprine. Lupus 14: 265–272

    Article  CAS  Google Scholar 

  18. Moroni G et al. (2006) A randomized pilot trial comparing cyclosporine and azathioprine for maintenance therapy in diffuse lupus nephritis over four years. Clin J Am Soc Nephrol 1: 925–932

    Article  CAS  Google Scholar 

  19. Chan TM et al. (2005) Long-term study of mycophenolate mofetil as continuous induction and maintenance treatment for diffuse proliferative lupus nephritis. J Am Soc Nephrol 16: 1076–1084

    Article  CAS  Google Scholar 

  20. Contreras G et al. (2004) Sequential therapies for proliferative lupus nephritis. N Engl J Med 350: 971–980

    Article  CAS  Google Scholar 

  21. Gottenberg JE et al. (2005) Tolerance and short term efficacy of rituximab in 43 patients with systemic autoimmune diseases. Ann Rheum Dis 64: 913–920

    Article  CAS  Google Scholar 

  22. Gunnarsson I et al. (2007) Histopathologic and clinical outcome of rituximab treatment in patients with cyclophosphamide-resistant proliferative lupus nephritis. Arthritis Rheum 56: 1263–1272

    Article  CAS  Google Scholar 

  23. Looney RJ et al. (2004) B cell depletion as a novel treatment for systemic lupus erythematosus: a phase I/II dose-escalation trial of rituximab. Arthritis Rheum 50: 2580–2589

    Article  CAS  Google Scholar 

  24. Ng KP et al. (2007) B cell depletion therapy in systemic lupus erythematosus: long-term follow-up and predictors of response. Ann Rheum Dis 66: 1259–1262

    Article  CAS  Google Scholar 

  25. Sfikakis PP et al. (2005) Remission of proliferative lupus nephritis following B cell depletion therapy is preceded by down-regulation of the T cell costimulatory molecule CD40 ligand: an open-label trial. Arthritis Rheum 52: 501–513

    Article  CAS  Google Scholar 

  26. Smith KG et al. (2006) Long-term comparison of rituximab treatment for refractory systemic lupus erythematosus and vasculitis: remission, relapse, and re-treatment. Arthritis Rheum 54: 2970–2982

    Article  CAS  Google Scholar 

  27. Tanaka Y et al. (2007) A multicenter phase I/II trial of rituximab for refractory systemic lupus erythematosus. Mod Rheumatol 17: 191–197

    Article  CAS  Google Scholar 

  28. Vigna-Perez M et al. (2006) Clinical and immunological effects of rituximab in patients with lupus nephritis refractory to conventional therapy: a pilot study. Arthritis Res Ther 8: R83

    Article  Google Scholar 

  29. Genentech Inc. website [http://www.gene.com/gene/news] (accessed 17 July 2008)

  30. A study to evaluate the efficacy and safety of rituximab in patients with severe systemic lupus erythematosus (EXPLORER) [http://clinicaltrials.gov/ct/show/NCT00137969] (accessed 17 July 2008)

  31. Study to evaluate the efficacy and safety of rituximab in subjects with ISN/RPS class III or IV lupus nephritis (LUNAR) [http://clinicaltrials.gov/ct/show/NCT00282347] (accessed 17 July 2008)

  32. Ogawa H et al. (2007) Prospective study of low-dose cyclosporine A in patients with refractory lupus nephritis. Mod Rheumatol 17: 92–97

    Article  CAS  Google Scholar 

  33. Mok CC et al. (2005) Tacrolimus for induction therapy of diffuse proliferative lupus nephritis: an open-labeled pilot study. Kidney Int 68: 813–817

    Article  CAS  Google Scholar 

  34. Mok CC et al. (2004) Treatment of pure membranous lupus nephropathy with prednisone and azathioprine: an open-label trial. Am J Kidney Dis 43: 269–276

    Article  CAS  Google Scholar 

  35. Moroni G et al. (1998) Treatment of membranous lupus nephritis. Am J Kidney Dis 31: 681–686

    Article  CAS  Google Scholar 

  36. Spetie DN et al. (2004) Mycophenolate therapy of SLE membranous nephropathy. Kidney Int 66: 2411–2415

    Article  CAS  Google Scholar 

  37. Austin H et al. (2004) Lupus membranous nephropathy: controlled trial of prednisone, pulse cyclophosphamide and cyclosporine A [abstract]. J Am Soc Nephrol 15: 54A

    Google Scholar 

  38. Kapitsinou PP et al. (2004) Lupus nephritis: treatment with mycophenolate mofetil. Rheumatology (Oxford) 43: 377–380

    Article  CAS  Google Scholar 

  39. Karim MY et al. (2005) Reduction of proteinuria with mycophenolate mofetil in predominantly membranous lupus nephropathy. Rheumatology (Oxford) 44: 1317–1321

    Article  CAS  Google Scholar 

  40. Borba EF et al. (2006) Mycophenolate mofetil is effective in reducing lupus glomerulonephritis proteinuria. Rheumatol Int 12: 1078–1083

    Article  Google Scholar 

  41. Tse KC et al. (2007) A pilot study on tacrolimus treatment in membranous or quiescent lupus nephritis with proteinuria resistant to angiotensin inhibition or blockade. Lupus 16: 46–51

    Article  CAS  Google Scholar 

  42. Nikpour M et al. (2005) Premature atherosclerosis in systemic lupus erythematosus. Rheum Dis Clin North Am 31: 329–354

    Article  Google Scholar 

  43. Bertsias GK et al. (2008) EULAR recommendations for the management of systemic lupus erytematosus. Report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics. Ann Rheum Dis 67: 195–205

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. G Bertsias is a Senior Fellow in the Department of Rheumatology and DT Boumpas is Professor of Medicine and Chief of the Department of Internal Medicine, Rheumatology, Clinical Immunology and Allergy in the University of Crete Medical School, Heraklion, Greece.,

    George Bertsias & Dimitrios T Boumpas

Authors
  1. George Bertsias
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dimitrios T Boumpas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dimitrios T Boumpas.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bertsias, G., Boumpas, D. Update on the management of lupus nephritis: let the treatment fit the patient. Nat Rev Rheumatol 4, 464–472 (2008). https://doi.org/10.1038/ncprheum0896

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncprheum0896

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing