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  • Review Article
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Treatment of idiopathic membranous nephropathy

Nature Reviews Nephrology volume 9, pages 443–458 (2013)Cite this article

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Abstract

Immunosuppressive treatment of patients with idiopathic membranous nephropathy (iMN) is heavily debated. The controversy is mainly related to the toxicity of the therapy and the variable natural course of the disease—spontaneous remission occurs in 40–50% of patients. The 2012 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Glomerulonephritis provides guidance for the treatment of iMN. The guideline suggests that immunosuppressive therapy should be restricted to patients with nephrotic syndrome and persistent proteinuria, deteriorating renal function or severe symptoms. Alkylating agents are the preferred therapy because of their proven efficacy in preventing end-stage renal disease. Calcineurin inhibitors can be used as an alternative although efficacy data on hard renal end points are limited. In this Review, we summarize the KDIGO guideline and address remaining areas of uncertainty. Better risk prediction is needed to identify patients who will benefit from immunosuppressive therapy, and the optimal timing and duration of this therapy is unknown because most of the randomized controlled trials were performed in low-risk or medium-risk patients. Alternative therapies, directed at B cells, are under study. The discovery of anti-M type phospholipase A2 receptor-antibodies is a major breakthrough and we envisage that in the near future, antibody-driven therapy will enable more individualized treatment of patients with iMN.

Key Points

  • Immunosuppressive treatment of idiopathic membranous nephropathy (iMN) should be restricted to patients at high risk of developing end-stage renal disease (ESRD)

  • Current tools for predicting prognosis in iMN are inaccurate and up to one-third of patients may receive unnecessary treatment—better risk predictors are required

  • The KDIGO guideline suggests use of alkylating agents as a first-line therapy because of their proven efficacy in preventing ESRD, calcineurin inhibitors are an alternative option

  • Less-toxic, alternative immunosuppressive therapies, such as rituximab, that could potentially be used to treat patients with iMN are currently being evaluated in randomized controlled trials with hard renal end points

  • In the near future, antibody-driven therapies may enable more individualized treatment of patients with anti-PLA2R-related membranous nephropathy

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Figure 1: Treatment algorithm for membranous nephropathy based on the 2012 Kidney Disease: Improving Global Outcomes guideline.11
Figure 2: Potential role of anti-PLA2R antibody assessment in guiding diagnosis and therapy in membranous nephropathy.

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Acknowledgements

J. M. Hofstra and J. F. M. Wetzels are supported by Dutch Kidney Foundation grants (NSN grants KJPB11.021 and OW08). F. C. Fervenza has received grant support from the Fulk Family Foundation.

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Authors and Affiliations

  1. Department of Nephrology, Radboud University Nijmegen Medical Center, PO Box 9101, Nijmegen, 6500 HB, Netherlands

    Julia M. Hofstra & Jack F. M. Wetzels

  2. Department of Nephrology and Hypertension, Mayo Clinic, Rochester, 200 First Street SW, Rochester, 55905, MN, USA

    Fernando C. Fervenza

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  1. Julia M. Hofstra
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  2. Fernando C. Fervenza
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  3. Jack F. M. Wetzels
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Contributions

J. M. Hofstra researched data for the article and wrote the manuscript. J. F. M. Wetzels wrote and reviewed and/or edited the manuscript before submission. F. C. Fervenza reviewed and/or edited the manuscript before submission. All authors made a substantial contribution to discussions of the content.

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Correspondence to Julia M. Hofstra.

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Hofstra, J., Fervenza, F. & Wetzels, J. Treatment of idiopathic membranous nephropathy. Nat Rev Nephrol 9, 443–458 (2013). https://doi.org/10.1038/nrneph.2013.125

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