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Rituximab for membranous nephropathy and immune disease: less might be enough

Nature Clinical Practice Nephrology volume 5, pages 76–77 (2009)Cite this article

Rituximab is a chimeric monoclonal antibody that targets the CD20 antigen of B cells and was first introduced in late 1990s for the treatment of B-cell proliferative disorders. Therapeutic use of rituximab has progressively been extended to immune diseases that might be caused by uncontrolled B-cell activation. One of the first experiences of rituximab use outside of B-cell proliferative disorders involved eight patients with idiopathic membranous nephropathy (IMN) and persistent nephrotic syndrome without previous spontaneous or treatment-induced remission.1 Rituximab promptly depleted circulating B cells, an effect that was sustained over time and was associated with a significant and persistent reduction of proteinuria and stabilization of kidney function over 1 year of follow-up.1,2 The treatment was safe and well tolerated by all patients. Subsequent reports confirmed and extended these encouraging, albeit preliminary, data,3 and consistently indicated that rituximab therapy might be a valuable alternative to drugs such as steroids, alkylating agents and other immunosuppressants that have been used extensively to treat IMN over the past 30 years but have failed to appreciably improve long-term patient or renal survival.4

Advances in the understanding of pathogenic mechanisms of disease in IMN are important to enable the design of more-specific approaches that are more likely to be effective and safe in the long term. IMN is an immune-mediated disease that results from the deposition of immunoglobulin G and complement components on the subepithelial layer of the glomerular capillary wall. Production of nephritogenic immunoglobulins by B cells is one of the earliest steps that underly renal dysfunction in IMN. Thus, although IMN autoantigens remain elusive and the role of B cells has not been fully explained in humans, agents that specifically interfere with B cells might represent the ideal first step towards selective therapy. In this regard, it is interesting to note that reduction of proteinuria was closely associated with profound depletion of circulating CD20+ B cells in patients with IMN who received rituximab therapy.1,2 Moreover, in the rare patients who relapse after a first course of rituximab, recurrence of proteinuria was invariably heralded by the reappearance of CD20+ cells in the circulation and further rituximab treatment induced remission by their depletion. These findings indicate that disruption of autoreactive B-cell clones and, conceivably, inhibited synthesis of nephritogenic antibodies, might explain, at least in part, the effect of rituximab in IMN.1,2,3 This mechanism, and others such as the inhibition of the antigen-presenting function of B cells and of T-cell activation, might play a role in other clinical conditions in which rituximab therapy is reported to be of benefit, including focal and segmental glomerulosclerosis, mixed essential cryoglobulinemia, systemic lupus erythematosus (SLE), primary systemic vasculitis, pure red cell aplasia with anti-erythropoietin antibodies, and thrombotic thrombocytopenic purpura associated with ADAMTS13 autoantibodies.5

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Authors and Affiliations

  1. P Ruggenenti is Director of the Renal Medicine Department at the Mario Negri Institute for Pharmacological Research and Assistant Professor in the Unit of Nephrology at Azienda Ospedaliera Ospedali Riuniti di Bergamo, P Cravedi is a Clinical Researcher at the Mario Negri Institute for Pharmacological Research and G Remuzzi is Director of the Clinical Research Center for Rare Diseases “Aldo e Cele Daccò” at the Mario Negri Institute for Pharmacological Research, and Director of the Unit of Nephrology at Azienda Ospedaliera Ospedali Riuniti di Bergamo, Bergamo, Italy.,

    Piero Ruggenenti, Paolo Cravedi & Giuseppe Remuzzi

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  1. Piero Ruggenenti
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  3. Giuseppe Remuzzi
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Correspondence to Giuseppe Remuzzi.

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The authors declare no competing financial interests.

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Ruggenenti, P., Cravedi, P. & Remuzzi, G. Rituximab for membranous nephropathy and immune disease: less might be enough. Nat Rev Nephrol 5, 76–77 (2009). https://doi.org/10.1038/ncpneph1007

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