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Successful treatment of steroid-resistant nephrotic syndrome associated with WT1 mutations

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Abstract

The Wilms’ tumor suppressor gene 1 (WT1) encodes a transcription factor involved in kidney and gonadal development. WT1 is also a key regulator of podocyte functions and mutations have been found in a small percentage of children with isolated or syndromal steroid-resistant nephrotic syndrome. It is commonly assumed that the nephrotic syndrome (NS) in patients with WT1 mutations is unresponsive to therapy and characterized by rapid progression to end-stage renal disease. We report long-term observations in 3 children with focal–segmental glomerulosclerosis associated with WT1 mutations and NS (2 cases) or nephrotic range proteinuria (1 case). All patients showed a favorable response to an intensified therapy consisting of cyclosporin A (CyA) in combination with induction therapy with intravenous and oral prednisone. Treatment with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers was added to the regimen at various times. As shown both by the short-term response and during long-term follow-up, this treatment resulted in clinical remission of the NS and/or significant reduction of proteinuria, while normal renal function could be maintained over many years. Thus, glomerular diseases in selected patients with mutations in genes regulating renal development and podocyte function may respond to combination therapy with CyA and corticosteroids.

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Acknowledgements

J.G. and U.Q. wish to thank Prof. B. Royer-Pokora and Dr. Valerie Schuhmacher (Heinrich-Heine Universität, Düsseldorf, Germany) for performing the WT1 mutation screening in patients 1 and 2.

C.J.S. and A.M. wish to thank Prof. E. Kanavakis, Dr. J. Traeger-Synodinos, and E. Fylaktou in the Department of Medical Genetics, Athens University, Greece, for facilitating the molecular characterization in patient 3.

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Authors and Affiliations

  1. Department of Pediatric Nephrology, Charité Berlin, Augustenburger Platz 1, 13353, Berlin, Germany

    Jutta Gellermann & Uwe Querfeld

  2. Department of Pediatric Nephrology, “P. & A. Kyriakou” Children’s Hospital, Levadias and Thivon Str, Goudi, Athens, Greece

    Constantinos J. Stefanidis & Andromachi Mitsioni

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  1. Jutta Gellermann
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  2. Constantinos J. Stefanidis
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  3. Andromachi Mitsioni
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  4. Uwe Querfeld
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Correspondence to Jutta Gellermann.

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Gellermann, J., Stefanidis, C.J., Mitsioni, A. et al. Successful treatment of steroid-resistant nephrotic syndrome associated with WT1 mutations. Pediatr Nephrol 25, 1285–1289 (2010). https://doi.org/10.1007/s00467-010-1468-3

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  • DOI: https://doi.org/10.1007/s00467-010-1468-3

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