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Monoclonal antibodies for podocytopathies: rationale and clinical responses

Nature Reviews Nephrology volume 5, pages 337–348 (2009)Cite this article

Abstract

The podocytopathies, including minimal-change nephropathy, focal segmental glomerulosclerosis, collapsing glomerulopathy, and diffuse mesangial sclerosis, involve diverse types of injury to podocytes. These injuries can have genetic causes, or can be caused by viral infection, mechanical stress, medication or—probably—immunologic injury. Several lines of evidence—including the immunosuppressive effects of standard therapies—suggest a role for immunologic injury in some cases, but the precise pathologic mechanisms are far from clear. Despite this uncertainty, newly available biologic therapies that target immune cells and cytokines have been used to treat a number of patients with different podocytopathies. Of these therapies, the greatest experience has been gained with rituximab. The data on all such therapies remain too fragmentary to provide firm conclusions, but further clinical research with such agents might help to define pathogenetic pathways and could potentially contribute to new therapies.

Key Points

  • The immunopathogenesis of idiopathic podocyte disease remains uncertain

  • Current immunosuppressive treatments for podocytopathies are nonspecific and potentially toxic

  • Monoclonal antibodies might help to elucidate the pathogenesis of podocytopathies and might also be useful for treatment of these diseases

  • At present, the use of monoclonal antibodies other than rituximab to treat podocytopathies has been very limited

  • Rituximab therapy has been associated with remission in cases of minimal-change nephropathy and focal segmental glomerulosclerosis

  • Occasional reports have shown remission of idiopathic nephrotic syndrome following treatment with tumor necrosis factor antagonists

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Figure 1: Biologic therapies and the immune system.

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Acknowledgements

The authors would like to thank Dr. Paolo Cravedi and Dr. Meryl Waldman for critical reading of the manuscript. Our work is supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.

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  1. Unit of Nephrology, Azienda Ospedaliera Ospedali Riuniti, Bergamo, Italy

    Maddalena Marasà

  2. Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA

    Jeffrey B. Kopp

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Marasà, M., Kopp, J. Monoclonal antibodies for podocytopathies: rationale and clinical responses. Nat Rev Nephrol 5, 337–348 (2009). https://doi.org/10.1038/nrneph.2009.70

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