Skip to main content

Advertisement

SpringerLink
Log in

Remission and withdrawal of therapy in lupus nephritis

  • Review
  • Published:
Journal of Nephrology Aims and scope Submit manuscript

Abstract

There is agreement that early diagnosis and aggressive treatment of lupus nephritis exacerbations are of paramount importance to achieve remission and prevent the development of irreversible lesions. There is less agreement about the optimal duration of maintenance treatment. Instead, the prolonged exposure to corticosteroids and/or immunosuppressive drugs can cause invalidating or even life-threatening complications. It is still unclear if these drugs can be safely withdrawn in lupus patients. We were able to completely withdraw therapy in around 1/3 of our patients after a follow-up of 5 years or more; 60 % of them never had to start therapy again. Based on our own experience, discontinuation of therapy should be applied only in selected cases, i.e. patients who received maintenance therapy for at least 5 years and are in complete renal remission for at least 3 years. Antimalarial agents are helpful in maintaining the remission after withdrawal of therapy. However, to achieve these goals, drugs should be tapered off very slowly and under strict surveillance. If all these prerequisites are satisfied, the withdrawal of therapy in patients with lupus nephritis may be considered safe, may improve the patients’ quality of life and may reduce the damage accrual.

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

Access this article

Log in via an institution

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

  1. Bertsias GK, Tektonidou M, Amoura Z, Aringer M, Bajema I, Berden JH, Boletis J et al (2012) Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. Ann Rheum 71:1771–1782

    Article  CAS  Google Scholar 

  2. Ponticelli C, Glassock RJ, Moroni G (2010) Induction and maintenance therapy in proliferative lupus nephritis. J Nephrol 23:9–16

    CAS  PubMed  Google Scholar 

  3. Moroni G, Raffiotta F, Trezzi B, Giglio E, Mezzina N, Del Papa N, Meroni P et al (2014) Rituximab vs mycophenolate and vs cyclophosphamide pulses for induction therapy of active lupus nephritis: a clinical observational study. Rheumatology (Oxford) 53:1570–1577

    Article  Google Scholar 

  4. Contreras G, Pardo V, Leclercq B, Lenz O, Tozman E, O’Nan P, Roth D (2004) Sequential therapies for proliferative lupus nephritis. N Engl J Med 350:971–980

    Article  CAS  PubMed  Google Scholar 

  5. Tamirou F, D'Cruz D, Sangle S, Remy P, Vasconcelos C, Fiehn C, Ayala Guttierez Mdel M, Gilboe IM, Tektonidou M, Blockmans D, Ravelingien I, le Guern V, Depresseux G, Guillevin L, Cervera R, Houssiau FA; MAINTAIN Nephritis Trial Group (2016) Long-term follow-up of the MAINTAIN Nephritis Trial, comparing azathioprine and mycophenolate mofetil as maintenance therapy of lupus nephritis. Ann Rheum Dis 75:526–531

    Article  PubMed  Google Scholar 

  6. Dooley MA, Jayne D, Ginzler EM, Isenberg D, Olsen NJ, Wofsy D, Eitner F, ALMS Group et al (2011) Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis. N Engl J Med 365:1886–1895

    Article  CAS  PubMed  Google Scholar 

  7. Moroni G, Doria A, Mosca A, Alberighi OD, Ferraccioli G, Todesco S, Manno C et al (2006) A randomized pitol trial comparing cyclosporin and azathioprine for maintenance therapy of diffuse lupus nephritis over four years. Clin J Am Soc Nephrol 5:925–932

    Article  Google Scholar 

  8. Ioannidis JP, Boki KA, Katsorida ME, Drosos AA, Skopouli FN, Boletis JN, Moutsopoulos HM (2000) Remission, relapse, and re-remission of proliferative lupus nephritis treated with cyclophosphamide. Kidney Int 57:258–264

    Article  CAS  PubMed  Google Scholar 

  9. Houssiau FA, Vasconcelos C, D’Cruz D, Sebastiani GD, de Ramon Garrido E, Danieli MG, Abramovicz D et al (2010) The 10-year follow-up data of the Euro-Lupus Nephritis Trial comparing low-dose and high-dose intravenous cyclophosphamide. Ann Rheum Dis 69:61–64

    Article  CAS  PubMed  Google Scholar 

  10. Moroni G, Quaglini S, Gallelli B, Banfi G, Messa P, Ponticelli C (2007) The long-term outcome of 93 patients with proliferative lupus nephritis. Nephrol Dial Transplant 22:2531–2539

    Article  PubMed  Google Scholar 

  11. Renal Disease Subcommittee of the American College of Rheumatology Ad Hoc Committee on Systemic Lupus Eryhthematosus Response Criteria (2006) The American College of Rheumatology response criteria for proliferative and membranous renal disease in systemic lupus eryhematosus clinical trials. Arthritis Rheum 54:421–432

    Article  Google Scholar 

  12. Petri M, Orbai AM, Alarcón GS, Gordon C, Merrill JT, Fortin PR, Bruce IN et al (2012) Derivation and validation of the systemic lupus international collaborating clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 64:2677–2686

    Article  PubMed  PubMed Central  Google Scholar 

  13. Castrejón I, Tani C, Jolly M, Huang A, Mosca M (2014) Indices to assess patients with systemic lupus erythematosus in clinical trials, long-term observational studies, and clinical care. Clin Exp Rheumatol 32:S-85–S-95

  14. Pons-Estel BA, Catoggio LJ, Cardiel MH, Soriano ER, Gentiletti S, Villa AR et al (2004) The GLADEL multinational Latin American prospective inception cohort of 1,214 patients with systemic lupus erythematosus: the GLADEL multinational Latin American prospective inception cohort of 1,214 patients with systemic lupus erythematosus: ethnic and disease heterogeneity among “Hispanics”. Medicine 83:1–17

    Article  PubMed  Google Scholar 

  15. Steiman AJ, Urowitz MB, Ibañez D, Papneja A, Gladman DD (2014) Prolonged clinical remission in patients with systemic lupus erythematosus. J Rheumatol 41:1808–1816

    Article  PubMed  Google Scholar 

  16. Zen M, Iaccarino L, Gatto M, Bettio S, Nalotto L, Ghirardello A, Punzi L, Doria A (2015) Prolonged remission in Caucasian patients with SLE: prevalence and outcomes. Ann Rheum Dis 74:2117–2122. doi:10.1136/annrheumdis-2015-207347

    Article  PubMed  Google Scholar 

  17. Moroni G, Quaglini S, Radice A, Trezzi B, Raffiotta F, Messa P, Sinico RA (2015) The value of a panel of autoantibodies for predicting the activity of lupus nephritis at time of renal biopsy. J Immunol Res 2015:106904. doi:10.1155/2015/106904

    Article  PubMed  PubMed Central  Google Scholar 

  18. Moroni G, Trendelenburg M, Del Papa N, Quaglini S, Raschi E, Panzeri P et al (2001) Anti-C1q antibodies may help in diagnosing a renal flare in lupus nephritis. Am J Kidney Dis 37:490–498

    Article  CAS  PubMed  Google Scholar 

  19. Birmingham DJ, Bitter JE, Ndukwe EG, Dials S, Gullo TR, Conroy S, Nagaraja HN, Rovin BH, Hebert LA (2016) Relationship of circulating Anti-C3b and Anti-C1q IgG to lupus nephritis and its flare. Clin J Am Soc Nephrol. 2016(11):47–53

    Article  Google Scholar 

  20. Fatemi A, Samadi G, Sayedbonakdar Z, Smiley A (2016) Anti-C1q antibody in patients with lupus nephritic flare: 18-month follow-up and a nested case-control study. Mod Rheumatol 26:233–239

    Article  CAS  PubMed  Google Scholar 

  21. Bock M, Heijnen I, Trendelenburg M (2015) Anti-C1q antibodies as a follow-up marker in SLE patients. PLoS ONE 10(4):e0123572

    Article  PubMed  PubMed Central  Google Scholar 

  22. Balow JE (2005) Clinical presentation and monitoring of lupus nephritis. Lupus. 14:25–30

    Article  CAS  PubMed  Google Scholar 

  23. Chen YE, Korbet SM, Katz RS, Schwartz MM, Lewis EJ, Collaborative Study Group (2008) Value of a complete or partial remission in severe lupus nephritis. Clin J Am Soc Nephrol 3:46–53

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Illei GG, Takada K, Parkin D, Austin HA, Crane M, Yarboro CH 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  PubMed  Google Scholar 

  25. Fernandes das Neves M, Irlapati RV, Isenberg D (2015) Assessment of long-term remission in lupus nephritis patients: a retrospective analysis over 30 years. Rheumatology 54:1403–1407

    Article  PubMed  Google Scholar 

  26. Ward MM (1999) Premature morbidity from cardiovascular and cerebrovascular diseases in women with systemic lupus erythematosus. Arthritis Rheum 42:338–346

    Article  CAS  PubMed  Google Scholar 

  27. Thamer M, Hernan MA, Zhang Y, Cotter D, Petri M (2009) Prednisone, lupus activity, and permanent organ damage. J Rheumatol 36:560–564

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Walsh M, Jayne D, Moist L, Tonelli M, Pannu N, Mans B (2010) Practice pattern variation in oral glucocorticoid therapy after the induction of response in proliferative lupus nephritis. Lupus 19:628–633

    Article  CAS  PubMed  Google Scholar 

  29. Condon MB, Ashby D, Pepper RJ, Cook HT, Levy JB, Griffith M, Cairns TD, Lightstone L (2013) Prospective observational single-centre cohort study to evaluate the effectiveness of treating lupus nephritis with rituximab and mycophenolate mofetil but no oral steroids. Ann Rheum Dis 72:1280–1286

    Article  CAS  PubMed  Google Scholar 

  30. Roccatello D, Sciascia S, Rossi D, Alpa M, Naretto C, Baldovino S, Menegatti E, La Grotta R, Modena V (2011) Intensive short-term treatment with rituximab, cyclophosphamide and methylprednisolone pulses induces remission in severe cases of SLE with nephritis and avoids further immunosuppressive maintenance therapy. Nephrol Dial Transplant 26:3987–3989

    Article  CAS  PubMed  Google Scholar 

  31. Pablos JL, Gutierrez-Millet V, Gomez-Reino JJ (1994) Remission of lupus nephritis with cyclophosphamide and late relapses following therapy withdrawal. Scand J Rheumatol 23:142–144

    Article  CAS  PubMed  Google Scholar 

  32. Mosca M, Neri R, Giannessi S, Pasquariello A, Puccini R, Bencivelli W, Bombardieri S (2001) Therapy with pulse methylprednisolone and short course pulse cyclophosphamide for diffuse proliferative glomerulonephritis. Lupus 10:253–257

    Article  CAS  PubMed  Google Scholar 

  33. Euler HH, Schroeder JO, Harten P, Zeuner RA, Gutschmidt HJ (1994) Treatment-free remission in severe systemic lupus erythematosus following synchronization of plasmapheresis with subsequent pulse cyclophosphamide. Arthritis Rheum 37:1784–1794

    Article  CAS  PubMed  Google Scholar 

  34. Drenkard C, Villa AR, Garcia-Padilla C, Pérez-Vázquez ME, Alarcón-Segovia D (1996) Remission of systematic lupus erythematosus. Medicine (Baltimore) 75:88–98

    Article  CAS  Google Scholar 

  35. Ponticelli C, Moroni G, Banfi G (1988) Discontinuation of therapy in diffuse proliferative lupus nephritis. Am J Med 85:275

    Article  CAS  PubMed  Google Scholar 

  36. Moroni G, Gallelli B, Quaglini S, Banfi G, Rivolta E, Messa P, Ponticelli C (2006) Withdrawal of therapy in patients with proliferative lupus nephritis: long-term follow-up. Nephrol Dial Transplant 21:1541–1548

    Article  CAS  PubMed  Google Scholar 

  37. Moroni G, Longhi S, Giglio E, Messa P, Ponticelli C (2013) What happens after complete withdrawal of therapy in patients with lupus nephritis. Clin Exp Rheumatol 31:S75–81

    PubMed  Google Scholar 

  38. Lee SJ, Silverman E, Bargman JM (2011) The role of antimalarial agents in the treatment of SLE and lupus nephritis. Nat Rev Nephrol 7:718–729

    Article  CAS  PubMed  Google Scholar 

  39. No authors listed (1991) A randomized study of the effect of withdrawing hydroxychloroquine sulfate in systemic lupus erythematosus. The Canadian Hydroxychloroquine Study Group. N Engl J Med 324;150–154

  40. Aptekar RG, Decker JL, Steinberg AD (1972) Exacerbation of SLE nephritis after cyclophosphamide withdrawal. N Engl J Med 286:1159–1160

    CAS  PubMed  Google Scholar 

  41. Sharon E, Kaplan D, Diamond HS (1973) Exacerbation of systemic lupus erythematosus after withdrawal of azathioprine therapy. N Engl J Med 288:122–124

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Unità Operativa di Nefrologia e Dialisi, Fondazione IRCCS Cà Granda Ospedale Policlinico Milano, Via della Commenda 15, 20122, Milano, Italy

    Gabriella Moroni, Francesca Raffiotta & Claudio Ponticelli

  2. Nephrology Unit, Clinical and Research Center Humanitas, Rozzano, Milano, Italy

    Claudio Ponticelli

Authors
  1. Gabriella Moroni
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Francesca Raffiotta
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Claudio Ponticelli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gabriella Moroni.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in this study were in accordance with the ethical standards of the institutional research committees and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Statement of human rights

For this type of study, formal consent is not required.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Moroni, G., Raffiotta, F. & Ponticelli, C. Remission and withdrawal of therapy in lupus nephritis. J Nephrol 29, 559–565 (2016). https://doi.org/10.1007/s40620-016-0313-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40620-016-0313-6

Keywords

Search

Navigation