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  • Review Article
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Recommendations and guidelines for the diagnosis and treatment of Fabry nephropathy in adults

Nature Clinical Practice Nephrology volume 4, pages 327–336 (2008)Cite this article

Abstract

Progressive loss of kidney function complicates Fabry disease, an X-linked lysosomal storage disorder that arises from deficiency of α-galactosidase activity. Heterozygous females with Fabry disease can be as severely affected as hemizygous males, who have the classic form of the disease. Enzyme-replacement therapy with recombinant human α-galactosidase clears the glycosphingolipid globotriaosylceramide from kidney cells, and can stabilize renal function in adults with mild to moderate Fabry nephropathy. However, adults with more advanced nephropathy and overt proteinuria do not respond as well. For these patients, antiproteinuric therapy given in conjunction with enzyme-replacement therapy might prevent further decline in kidney function. In this Review, we propose guidelines and recommendations for the diagnosis and management of Fabry nephropathy in adults, based on published data and on the consensus of opinion of participants in the 7th International Fabry Nephropathy Roundtable in 2007. These organ-specific guidelines could be easier to implement than general guidelines, provided they are used in the context of an overall multisystem care approach.

Key Points

  • Fabry nephropathy is an important cause of morbidity and mortality in males with classic disease, as well as in an appreciable number of females

  • Without suitable screening, Fabry nephropathy can be overlooked; kidney biopsy can confirm the diagnosis, stage the severity of the disease, and gauge the response to therapy

  • Enzyme-replacement therapy (ERT) clears globotriaosylceramide from many kidney cell types, and long-term ERT stabilizes renal function in adults with mild to moderate renal impairment, but it does not decrease proteinuria; patients with more advanced nephropathy respond less well

  • ERT should be started as early as possible to delay further organ damage, especially in males with no residual enzyme activity

  • Proteinuria is an important therapeutic target; adjunctive treatment with angiotensin-converting-enzyme inhibitors and/or angiotensin-receptor blockers should be used to reduce urinary total protein excretion to less than 500 mg/day

  • Further studies are needed to define the optimal diagnostic, follow-up and treatment protocols for Fabry nephropathy and to provide an evidence base for current and future guidelines in adults and children

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Figure 1: The accepted model of Fabry disease progression.2
Figure 2: Prognostic influence of baseline proteinuria in patients with mild Fabry nephropathy (stage 1–2 chronic kidney disease) receiving enzyme-replacement therapy with agalsidase beta.10
Figure 3: Stabilization of eGFR in patients with Fabry nephropathy during use of enzyme-replacement therapy with agalsidase beta, plus ACE inhibitors and/or ARBs.50

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Acknowledgements

This Review is based on a discussion of the available evidence by an international panel of experts that met in June 2007 at the 7th International Fabry Nephropathy Roundtable, Barcelona, which was sponsored by Genzyme. The authors appreciate the assistance of Excerpta Medica in preparing the transcript of the roundtable. A Ortiz is supported by ISCIII-RETIC REDinREN/RD06/0016, Programa Intensificación Actividad Investigadora (ISCIII/Agencia Laín-Entralgo/CM).

Author information

Authors and Affiliations

  1. A Ortiz is Associate Chief of Nephrology at Fundación Jiménez Díaz and Associate Professor of Medicine at Universidad Autónoma de Madrid, Madrid, Spain;,

    Alberto Ortiz

  2. JP Oliveira is a Consultant Nephrologist in the Department of Nephrology and the Physician-in-Charge of the Medical Genetics Outpatient Clinic at the Hospital São João, Porto, Portugal;,

    João P Oliveira

  3. C Wanner is Chief of the Division of Nephrology and Professor of Medicine at the University of Würzburg, Germany;,

    Christoph Wanner

  4. BM Brenner is Director Emeritus of the Renal Division, Brigham and Women's Hospital, Boston, MA, USA;,

    Barry M Brenner

  5. S Waldek is a Consultant in Inherited Metabolic Diseases at Salford Royal NHS Foundation Trust, Manchester, UK; and,

    Stephen Waldek

  6. DG Warnock is Director of the Division of Nephrology and Professor of Medicine and Physiology at the University of Alabama at Birmingham, AL, USA.,

    David G Warnock

Authors
  1. Alberto Ortiz
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  4. Barry M Brenner
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  5. Stephen Waldek
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Corresponding author

Correspondence to Alberto Ortiz.

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Competing interests

A Ortiz is a member of the European Advisory Board of the Genzyme-sponsored Fabry Registry, acts as a consultant for Genzyme on Fabry disease, and has received honoraria from Genzyme for lectures. JP Oliveira is a member of the European Advisory Board of the Fabry Registry, and has received payment for lecture fees and support for research activities from Genzyme. C Wanner is a member of the European Advisory Board of the Fabry Registry, and has received lecture fees and support for research activities from Genzyme. BM Brenner is a Fabry disease consultant for, and has received honoraria for lectures from, Genzyme. S Waldek is a member of the European Advisory Board of the Fabry Registry, and has received lecture fees and support for research activities from Genzyme. DG Warnock is a member of the North American Advisory Board of the Fabry Registry, a consultant for Genzyme Corporation on Fabry disease, and has received honoraria for lectures and research grants from Genzyme.

Supplementary information

Supplementary Table 1

Clinical practice recommendations and guidelines for the management of Fabry nephropathy in adults. (DOC 59 kb)

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Ortiz, A., Oliveira, J., Wanner, C. et al. Recommendations and guidelines for the diagnosis and treatment of Fabry nephropathy in adults. Nat Rev Nephrol 4, 327–336 (2008). https://doi.org/10.1038/ncpneph0806

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