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  • Review Article
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Treatment of proliferative lupus nephritis: a slowly changing landscape

Nature Reviews Nephrology volume 7, pages 96–109 (2011)Cite this article

Abstract

Proliferative lupus nephritis is the most severe form of lupus nephritis. Outcomes of this disease are affected by ethnicity, clinical characteristics, irreversible damage on renal biopsy, initial response to treatment and future disease course (for example, the occurrence of renal flares). Initial intensive (induction) treatment of proliferative lupus nephritis is aimed at achieving remission, but optimal duration and intensity are not well defined. A combination of intravenous cyclophosphamide and corticosteroids have been shown to decrease the risk of end-stage renal disease, but are associated with substantial acute toxic effects (such as infections) and chronic toxic effects (such as ovarian failure). In white populations, low-dose cyclophosphamide is a reasonable alternative to high-dose cyclophosphamide as it is similarly effective and associated with less toxicity. Mycophenolate mofetil is as effective as high-dose intravenous cyclophosphamide in terms of inducing remission and similar in terms of safety. Although most patients respond to induction treatment, remission is often only achieved after patients are switched to maintenance treatment. As maintenance treatment, mycophenolate mofetil is superior to azathioprine and azathioprine is similarly effective to ciclosporin in terms of prevention or reducing the risk of relapse. Rituximab should be reserved for patients with refractory disease. Treatment of lupus nephritis should be individually tailored to patients, with more aggressive therapy reserved for patients at high risk of renal dysfunction and progression of renal disease.

Key Points

  • Proliferative lupus nephritis (class III [focal] and class IV [diffuse]) is the most severe form of lupus nephritis

  • Outcomes of patients with proliferative lupus nephritis improved dramatically following the introduction of corticosteroids and cyclophosphamide, but 25–30% of patients still develop end-stage renal disease over 20 years of follow-up

  • Slow onset of remission and the occurrence of renal flares are associated with an increased risk of later loss of renal function

  • As induction treatment, mycophenolate mofetil (MMF) is similarly effective to cyclophosphamide; however, cyclophosphamide may be inferior to MMF in black and Hispanic patients

  • As maintenance treatment, MMF is superior to azathioprine, and MMF and azathioprine are superior to intravenous cyclophosphamide pulses; in white patients, ciclosporin seems to be similarly effective to azathioprine

  • B-cell depletion with rituximab might be useful in patients with proliferative lupus nephritis that is refractory or intolerant to cyclophosphamide; the putative role of B-cell-targeted treatment in lupus nephritis requires further study

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Acknowledgements

The authors' work is supported by the research initiative of the Czech Ministry of Health (MZO 00023728).

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  1. Department of Nephrology, 1st School of Medicine and General University Hospital, Charles University, U Nemocnice 2, 128 08, Prague 2, Czech Republic

    Vladimir Tesar & Zdenka Hruskova

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  1. Vladimir Tesar
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V. Tesar and Z. Hruskova both contributed to researching data for the article, discussions of the content and the review/editing of the manuscript before submission. V. Tesar wrote the article.

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Correspondence to Vladimir Tesar.

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V. Tesar declares an association with the following company: Roche (speaker's bureau: honoraria). Z. Hruskova declares no competing interests.

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Tesar, V., Hruskova, Z. Treatment of proliferative lupus nephritis: a slowly changing landscape. Nat Rev Nephrol 7, 96–109 (2011). https://doi.org/10.1038/nrneph.2010.170

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