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  • Review Article
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Childhood nephrotic syndrome—current and future therapies

Nature Reviews Nephrology volume 8, pages 445–458 (2012)Cite this article

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Abstract

The introduction of corticosteroids more than 50 years ago dramatically improved the prognosis of children with nephrotic syndrome. Corticosteroids remain the standard initial treatment for children with this disease, but a considerable proportion of patients do not respond and are therefore at risk of progressing to end-stage renal disease. Because of this risk, new therapeutic strategies are needed for steroid-resistant nephrotic syndrome. These strategies have historically focused on identifying effective alternative immunosuppressive agents, such as ciclosporin and tacrolimus, yet evidence now indicates that nephrotic syndrome results from podocyte dysfunction. Even conventional immunosuppressive agents, such as glucocorticoids and ciclosporin, directly affect podocyte structure and function, challenging the 'immune theory' of the pathogenesis of childhood nephrotic syndrome in which disease is caused by T cells. This Review summarizes the currently available treatments for childhood nephrotic syndrome, and discusses selected novel pathways in podocytes that could be targeted for the development of next-generation treatments for children with this syndrome.

Key Points

  • Corticosteroids have been used to treat childhood nephrotic syndrome for more than 50 years but a minority of patients, especially those with focal segmental glomerulosclerosis, are resistant to this treatment

  • Evidence now suggests that childhood nephrotic syndrome is attributable to podocyte dysfunction; many medications used to treat childhood nephrotic syndrome target the immune system, but also directly affect podocytes

  • Several currently available agents developed for other diseases, such as diabetes, are now being considered for treatment of steroid-resistant childhood nephrotic syndrome

  • Ongoing research has identified a number of pathways occuring in podocytes that may be potential targets for future therapies to treat steroid-resistant childhood nephrotic syndrome

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Figure 1: Total rituximab dose does not seem to correlate with initial clinical response.
Figure 2: Oral galactose induces remission of proteinuria in an adult with nephrotic syndrome resistant to multiple immunosuppressive agents.
Figure 3: Schematic of the canonical and alternate modes of action of thiazolidinediones.
Figure 4: Following TGF-β binding, the TGF-β receptor is activated, resulting in downstream activation of pro-apoptotic p38 MAPK and MK2 signaling via activation of PKC.

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Authors and Affiliations

  1. Emory University, 2015 Uppergate Drive, Atlanta, 30322, GA, USA

    Larry A. Greenbaum

  2. Center for Clinical and Translational Research, The Research Institute at Nationwide Children's Hospital, 700 Children's Drive, Columbus, 43205, OH, USA

    Rainer Benndorf & William E. Smoyer

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Greenbaum, L., Benndorf, R. & Smoyer, W. Childhood nephrotic syndrome—current and future therapies. Nat Rev Nephrol 8, 445–458 (2012). https://doi.org/10.1038/nrneph.2012.115

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