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Genetic testing in nephrotic syndrome—challenges and opportunities

Nature Reviews Nephrology volume 9, pages 179–184 (2013)Cite this article

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Abstract

Monogenic nephrotic syndrome (nephrotic syndrome caused by a single gene defect) is responsible for only a small percentage of cases of nephrotic syndrome, but information from studies of the unique cohort of patients with this form of the disease has dramatically improved our understanding of the disease pathogenesis. The use of genetic testing in the management of children and adults with nephrotic syndrome poses unique challenges for clinicians in terms of who to test and how to use the information obtained from testing in the clinical setting. In our view, not enough data exist at present to justify the routine genetic testing of all patients with nephrotic syndrome. Testing is warranted, however, in patients with congenital nephrotic syndrome (onset at 0–3 months), infantile nephrotic syndrome (onset at 3–12 months), a family history of nephrotic syndrome, and those in whom nephrotic syndrome is associated with other congenital malformations. The family and/or the patient should be given complete and unbiased information on the potential benefits and risks associated with therapy, including the reported outcomes of treatment in patients with similar mutations. Based on the data available in the literature so far, intensive immunosuppressive treatment is probably not indicated in monogenic nephrotic syndrome if complete or partial remission has not been achieved within 6 weeks of starting treatment. We advocate that family members of individuals with genetic forms of nephrotic syndrome undergo routine genetic testing prior to living-related kidney transplantation. Prospective, multicentre studies are needed to more completely determine the burden of disease caused by monogenic nephrotic syndrome, and randomized controlled trials are needed to clarify the presence or absence of clinical responses of monogenic nephrotic syndrome to available therapies.

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Figure 1: Algorithm for genetic testing in nephrotic syndrome.

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Author information

Authors and Affiliations

  1. Department of Pediatrics and Center for Human Genetics, Duke University Medical Center, 2301 Erwin Road, Durham, 27710, NC, USA

    Rasheed A. Gbadegesin

  2. Center for Human Genetics and Department of Medicine, Duke University Medical Center, 2301 Erwin Road, Durham, 27710, NC, USA

    Michelle P. Winn

  3. Center for Clinical and Translational Research, The Research Institute at Nationwide Children's Hospital, 700 Children's Drive, W303, Columbus, 43205, OH, USA

    William E. Smoyer

Authors
  1. Rasheed A. Gbadegesin
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  2. Michelle P. Winn
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  3. William E. Smoyer
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The authors contributed equally to all aspects of this manuscript.

Corresponding author

Correspondence to William E. Smoyer.

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Competing interests

M. P. Winn declares an association with the following company: Athena Diagnostics (consultant). The other authors declare no competing interests.

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Gbadegesin, R., Winn, M. & Smoyer, W. Genetic testing in nephrotic syndrome—challenges and opportunities. Nat Rev Nephrol 9, 179–184 (2013). https://doi.org/10.1038/nrneph.2012.286

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