Intervention Review

Treatment for lupus nephritis

  1. Lorna Henderson1,*,
  2. Philip Masson2,
  3. Jonathan C Craig2,3,
  4. Robert S Flanc4,
  5. Matthew A Roberts5,
  6. Giovanni FM Strippoli2,3,6,7,8,
  7. Angela C Webster1,2,3

Editorial Group: Cochrane Renal Group

Published Online: 12 DEC 2012

Assessed as up-to-date: 15 APR 2012

DOI: 10.1002/14651858.CD002922.pub3

How to Cite

Henderson L, Masson P, Craig JC, Flanc RS, Roberts MA, Strippoli GFM, Webster AC. Treatment for lupus nephritis. Cochrane Database of Systematic Reviews 2012, Issue 12. Art. No.: CD002922. DOI: 10.1002/14651858.CD002922.pub3.

Author Information

  1. 1

    The University of Sydney at Westmead, Centre for Transplant and Renal Research, Westmead Millennium Institute, Westmead, NSW, Australia

  2. 2

    The University of Sydney, Sydney School of Public Health, Sydney, Australia

  3. 3

    The Children's Hospital at Westmead, Cochrane Renal Group, Centre for Kidney Research, Westmead, NSW, Australia

  4. 4

    Monash Medical Centre, Department of Nephrology, Clayton, VIC, Australia

  5. 5

    Austin Health, Department of Nephrology, Heidelberg, VIC, Australia

  6. 6

    University of Bari, Department of Emergency and Organ Transplantation, Bari, Italy

  7. 7

    Mario Negri Sud Consortium, Department of Clinical Pharmacology and Epidemiology, Santa Maria Imbaro, Italy

  8. 8

    Diaverum, Medical-Scientific Office, Lund, Sweden

*Lorna Henderson, Centre for Transplant and Renal Research, Westmead Millennium Institute, The University of Sydney at Westmead, Westmead, NSW, 2145, Australia. l_k_henderson@hotmail.com.

Publication History

  1. Publication Status: New search for studies and content updated (conclusions changed)
  2. Published Online: 12 DEC 2012

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Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary

Background

Cyclophosphamide, in combination with corticosteroids has been used to induce remission in proliferative lupus nephritis, the most common kidney manifestation of the multisystem disease, systemic lupus erythematosus. Cyclophosphamide therapy has reduced mortality from over 70% in the 1950s and 1960s to less than 10% in recent years. Cyclophosphamide combined with corticosteroids preserves kidney function but is only partially effective and may cause ovarian failure, infection and bladder toxicity. Several new agents, including mycophenolate mofetil (MMF), suggest reduced toxicity with equivalent rates of remission. This is an update of a Cochrane review first published in 2004.

Objectives

To assess the benefits and harms of different immunosuppressive treatments in biopsy-proven proliferative lupus nephritis.

Search methods

For this update, we searched the Cochrane Renal Group's Specialised Register (up to 15 April 2012) through contact with the Trials' Search Coordinator using search terms relevant to this review.

Selection criteria

Randomised controlled trials (RCTs) and quasi-RCTs comparing any treatments for biopsy-proven lupus nephritis in both adult and paediatric patients with class III, IV, V +III and V +IV lupus nephritis were included. All immunosuppressive treatments were considered.

Data collection and analysis

Data were abstracted and quality assessed independently by two authors, with differences resolved by discussion. Dichotomous outcomes were reported as risk ratio (RR) and measurements on continuous scales reported as mean differences (MD) with 95% confidence intervals (CI).

Main results

We identified 50 RCTs involving 2846 participants. Of these, 45 studies (2559 participants) investigated induction therapy, and six studies (514 participants), considered maintenance therapy.

Compared with intravenous (IV) cyclophosphamide, MMF was as effective in achieving stable kidney function (5 studies, 523 participants: RR 1.05, 95% CI 0.94 to 1.18) and complete remission of proteinuria (6 studies, 686 participants: RR 1.16, 95% CI 0.85 to 1.58). No differences in mortality (7 studies, 710 participants: RR 1.02, 95% CI 0.52 to 1.98) or major infection (6 studies, 683 participants: RR 1.11, 95% CI 0.74 to 1.68) were observed. A significant reduction in ovarian failure (2 studies, 498 participants: RR 0.15, 95% CI 0.03 to 0.80) and alopecia (2 studies, 522 participants: RR 0.22, 95% CI 0.06 to 0.86) was observed with MMF. In maintenance therapy, the risk of renal relapse (3 studies, 371 participants: RR 1.83, 95% CI 1.24 to 2.71) was significantly higher with azathioprine compared with MMF. Multiple other interventions were compared but outcome data were relatively sparse. Overall study quality was variable. The internal validity of the design, conduct and analysis of the included RCTs was difficult to assess in some studies because of the omission of important methodological details. No study adequately reported all domains of the risk of bias assessment so that elements of internal bias may be present.

Authors' conclusions

MMF is as effective as cyclophosphamide in inducing remission in lupus nephritis, but is safer with a lower risk of ovarian failure. MMF is more effective than azathioprine in maintenance therapy for preventing relapse with no increase in clinically important side effects. Adequately powered trials with long term follow-up are required to more accurately define the risks and eventual harms of specific treatment regimens.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary

Treatment for people with lupus nephritis

Lupus nephritis is an inflammatory condition affecting the kidneys which is caused by systemic lupus erythematosus (SLE), an autoimmune disease that is more common among women. About half of all people with SLE develop lupus nephritis, and of these about 1/10 experience chronic kidney disease or kidney failure. Treatment aims to delay disease progression and achieve remission by stabilising and improving kidney function and minimising side effects. For about the past 30 years, standard treatment for lupus nephritis has focused on a combination of cyclophosphamide (an alkylating agent) and corticosteroids.

We found that the drug mycophenolate mofetil (MMF) was as effective as cyclophosphamide in combination with corticosteroids in achieving remission in people with lupus nephritis. MMF has fewer harmful effects including ovarian failure, decreased ability to fight infections (leucopenia) and hair loss (alopecia). MMF was superior to azathioprine (an immunosuppressive drug) in combination with corticosteroids at preventing renal relapse when used as maintenance therapy.