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Cyclosporin therapy in patients with Alport syndrome

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Abstract

Alport syndrome (AS) is a hereditary disorder of type IV collagen characterized by the association of progressive hematuric nephritis and sensorineural hearing loss. An increase in proteinuria is linked with progressive renal failure. Preliminary data have shown that cyclosporin therapy reduces proteinuria, thereby suggesting that it may also slow the progression of AS nephropathy. We treated nine AS patients manifesting proteinuria >1 g/m2/day and a glomerular filtration rate (GFR) >50 ml/min/1.73 m2 with cyclosporin for at least 6 months. At the end of this 6-month period, mean proteinuria had decreased from 2±1.06 to 0.65±0.73 g/day, and mean albuminemia had increased from 29±5.2 to 35±6.5 g/l. Mean inulin clearance had decreased from 102±29 to 74±16.3 ml/min/1.73 m2. Cyclosporin treatment was stopped in four patients because of inefficacy or adverse effects and continued in the remaining five patients for an additional 14–42 months. At the end of this second treatment period, control renal biopsies revealed significant lesions of cyclosporin nephrotoxicity in three patients. Based on these results we conclude that while cyclosporin therapy can decrease proteinuria in most patients with AS, it may be associated with nephrotoxicity, thereby precluding its long-term use.

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Acknowledgements

We thank Novartis Pharma S.A. France, who provided Neoral for the patients.

We also thank Christine Hirth and François Chantrel (Institut de chimie biologique, Universite Louis Pasteur, Strasbourg, France) for technical assistance for the dextran clearance determinations.

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Authors and Affiliations

  1. Service de Néphrologie Pédiatrique, Hôpital Necker-Enfants Malades, 149 rue de sèvres, 75743, Paris Cedex 15, France

    Marina Charbit, Marie-France Gagnadoux & Patrick Niaudet

  2. Institut National de la Santé et de la Recherche Médicale, INSERM U574, Hôpital Necker-Enfants Malades, Paris, France

    Marie-Claire Gubler

  3. Service d’Explorations Fonctionnelles, Hôpital Necker-Enfants Malades, Paris, France

    Michèle Dechaux

  4. Service de Néphrologie, Hôpital Necker-Enfants Malades, Paris, France

    Jean-Pierre Grünfeld

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  1. Marina Charbit
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  2. Marie-Claire Gubler
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  3. Michèle Dechaux
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  4. Marie-France Gagnadoux
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  5. Jean-Pierre Grünfeld
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  6. Patrick Niaudet
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Correspondence to Patrick Niaudet.

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Charbit, M., Gubler, MC., Dechaux, M. et al. Cyclosporin therapy in patients with Alport syndrome. Pediatr Nephrol 22, 57–63 (2007). https://doi.org/10.1007/s00467-006-0227-y

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  • DOI: https://doi.org/10.1007/s00467-006-0227-y

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