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Treatment of severe lupus nephritis: the new horizon

Key Points

  • The objective of immunosuppressive treatment for lupus nephritis is to abate ongoing damage to nephrons by active disease, and to prevent disease flares during the long-term maintenance phase

  • Current standard of care induction therapy for active, severe proliferative or membranous lupus nephropathy is dual immunosuppression with high-dose corticosteroids and either mycophenolate mofetil or cyclophosphamide

  • Low-dose corticosteroids combined with either mycophenolate or azathioprine are recommended as maintenance immunosuppression; mycophenolate mofetil for a minimum of 2 years is preferred in patients with previous renal flares

  • The selection of immunosuppressive agent and dose should take into account ethnic variation in response to different treatments

  • Antimalarial treatment is associated with reductions in renal flares and accrual of renal damage, as well as improved patient survival

  • Holistic management of patients with lupus nephritis should include prevention of and surveillance for complications, blood pressure control, renal preservation, vascular risk minimization and attention to overall quality of life

Abstract

Lupus nephritis is a common and severe manifestation of systemic lupus erythematosus, and an important cause of both acute kidney injury and end-stage renal disease. Despite its aggressive course, lupus nephritis is amenable to treatment in the majority of patients. The paradigm of immunosuppressive treatment for lupus nephritis has evolved over the past few decades from corticosteroids alone to corticosteroids combined with cyclophosphamide. Sequential treatment regimens using various agents have been formulated for induction and long-term maintenance therapy, and mycophenolate mofetil has emerged as a standard of care option for both induction and maintenance immunosuppressive treatment. The current era has witnessed the emergence of multiple novel therapeutic options, such as calcineurin inhibitors and biologic agents that target key pathogenetic mechanisms of lupus nephritis. Clinical outcomes have improved in parallel with these therapeutic advances. This Review discusses the evidence in support of current standard of care immunosuppressive treatments and emerging therapies, and describes their roles and relative merits in the management of patients with lupus nephritis.

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Figure 1: Pathogenesis of lupus nephritis.
Figure 2: Biologic therapies for lupus nephritis.
Figure 3: Treatment algorithm for severe (class III–V) lupus nephritis.

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Acknowledgements

The author thanks the Wai Hung Charitable Foundation Limited, Mr G King, and the Yu Chiu Kwong Endowed Professorship in Medicine of The University of Hong Kong for their funding support of clinical research projects in lupus nephritis conducted at Queen Mary Hospital, Hong Kong.

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Correspondence to Tak Mao Chan.

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T.M.C. declares that he has acted as a consultant for the following companies: Astellas, Teva and Vifor Pharma.

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Chan, T. Treatment of severe lupus nephritis: the new horizon. Nat Rev Nephrol 11, 46–61 (2015). https://doi.org/10.1038/nrneph.2014.215

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