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Lessons from genetics: is it time to revise the therapeutic approach to children with steroid-resistant nephrotic syndrome?

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Abstract

Primitive nephrotic syndrome is one of the most common glomerular diseases in childhood and represents the clinical manifestation of various pathologic changes in the kidney. In children, nephrotic syndrome is classified based on the initial response to empiric corticosteroid treatment, which is considered as the best predictor of patients’ final outcome. The advent of next-generation sequencing technology showed that genetic alterations in structural genes of the podocyte can be recognized in a significant proportion of not only familial or syndromic patients with steroid-resistant nephrotic syndrome (SRNS), but also of sporadic cases, raising the question of whether it is time to update current protocols of patient care. In this review, we discuss the implications derived from several studies describing a high prevalence in children with SRNS of pathogenic mutations in a group of genes and their unresponsiveness to immunosuppressive therapy. We propose a diagnostic and therapeutic algorithm to reduce the exposure to immunosuppressants in individuals with unresponsive forms of the disease, sparing patients the untoward side effects of prolonged ineffective treatments, and at the same time guaranteeing the optimal immunosuppressive or other new therapy in potentially responsive patients.

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Acknowledgments

This article is supported by funding from the Meyer Children’s Hospital Foundation and from the Fondazione AMARTI to Paola Romagnani.

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Authors and Affiliations

  1. Nephrology and Dialysis Unit, Meyer Children’s Hospital, Florence, Italy

    Francesca Becherucci, Benedetta Mazzinghi & Paola Romagnani

  2. Medical Genetics Unit, Meyer Children’s Hospital, Florence, Italy

    Aldesia Provenzano & Sabrina Giglio

  3. Department of Pediatrics, University of Padua, Padua, Italy

    Luisa Murer

  4. Department of Biomedical Experimental and Clinical Sciences “Mario Serio”, University of Florence, Viale Pieraccini 6, 50139, Florence, Italy

    Sabrina Giglio & Paola Romagnani

Authors
  1. Francesca Becherucci
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  2. Benedetta Mazzinghi
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  6. Paola Romagnani
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Correspondence to Paola Romagnani.

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The results presented in this review have not been published previously in whole or part, except in the abstract format. All authors declare no conflict of interest.

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This article does not contain any studies with human participants performed by any of the authors.

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Becherucci, F., Mazzinghi, B., Provenzano, A. et al. Lessons from genetics: is it time to revise the therapeutic approach to children with steroid-resistant nephrotic syndrome?. J Nephrol 29, 543–550 (2016). https://doi.org/10.1007/s40620-016-0315-4

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  • DOI: https://doi.org/10.1007/s40620-016-0315-4

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