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Author Notes:

Correspondence and offprint requests to: Robert J. Desnick; E-mail: robert.desnick@mssm.edu

The authors are indebted to the patients whose data were included in this study, and to the physicians, nursing staffs and study coordinators who provided the patients’ care at all the investigational sites.

The authors would like to acknowledge the efforts of Hans Ebels (Genzyme Corporation) in assisting with the preparation of the manuscript for submission.

In particular, the authors would like to acknowledge the principal investigators at the study sites for their contributions: United States of America—J. Barranger, Pittsburgh, PA; K. Brandspiegel, Elizabeth City, NC; D. Brennan, St Louis, MO; J. Charrow, Chicago, IL; C.M. Eng, Houston, TX; R.W. Erbe, Buffalo, NY; P. Fernhoff, Atlanta, GA; R. Finkel, Philadelphia, PA; R. Hopkin, Cincinnati, OH; M.C. Leary, Boston, MA; C. Schmitt, Everett, WA; K.B. Sims, Boston, MA; R. Steiner, Portland, OR; J. Thomas, Denver CO; N. Weinreb, Coral Springs, FL; Czech Republic—S. Magage, Prague; Canada—D.G. Bichet, Montreal, QC; A. Chan, Edmonton, Alberta; J. Clarke, Toronto, Ontario; S. Dyack, Halifax, Novo Scotia; P. Wyatt, Toronto, Ontario.

Furthermore, the authors wish to thank the nursing staffs of the general clinical research centres at our institutions for their assistance with this study.

Genzyme Corporation supported data collection by Abt Associates Clinical Trials.

The authors wish to thank Fanny O’Brien, PhD (senior director of Biostatistics, BioMedical Operations, Genzyme Corporation) for statistical services.

Conflict of interest statement. R.S was partly funded by Shire Human Genetic Therapies and Amicus Therapeutics for research.

M.B. is a member of the Board of Advisors of the Fabry Registry and is compensated for the services by Genzyme Corporation, and has received speaking fees from Genzyme related to lysosomal storage disorders.

J.B. has nothing to disclose. G.E.L received reimbursement of expenses and small honoraria for lectures on the management of Fabry disease, from Genzyme Corporation, Shire Human Genetic Therapies and Actelion.

All honoraria are donated to the ‘Gaucher Stichting’, a national foundation that supports research in the field of lysosomal storage disorders.

S.P received research, educational and programmatic support from Genzyme Corporation. S.A.S. has been in receipt of honoraria, from Genzyme Corporation, for lectures on Fabry disease.

W.R.W. is a paid consultant for Genzyme Corporation and Amicus Therapeutics; has been in receipt of speaker fees from Genzyme Corporation, an unrestricted educational grant from Amicus Therapeutics, and research support from Genzyme Corporation and Amicus Therapeutics.

D.G.W. is a paid consultant for Genzyme Corporation, and has been in receipt of speaker fees and research support.

R.J.D. is consultant, research grantee and inventor of patents licensed to Genzyme Corporation, and consultant and founding stockholder of Amicus Therapeutics.

Subjects:

Research Funding:

This work was funded in part by grants from the National Center for Research Resources of the National Institutes of Health (NIH) grants to the General Clinical Research Centers at the Mount Sinai School of Medicine (5 M01 RR00071), Cedars-Sinai Medical Center (5 M01 RR00032), University of California, San Francisco (5 M01 RR01271), and University of Alabama at Birmingham (5 M01 RR00032).

These studies also were supported in part by the research program of the National Institute of Neurological Disorders and Stroke, and an NIH research grant (MERIT Award, 5 R37 DK34045) to R.J.D. WW was supported by the Winnick Family Clinical Development Scholar Award.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Transplantation
  • Urology & Nephrology
  • albuminuria
  • arrhythmia
  • Fabry disease
  • nephropathy
  • proteinuria
  • stroke
  • GLOMERULAR-FILTRATION-RATE
  • AGALSIDASE-BETA THERAPY
  • CLINICAL-MANIFESTATIONS
  • ALPHA-GALACTOSIDASE
  • OUTCOME SURVEY
  • CONTROLLED TRIAL
  • RENAL-FUNCTION
  • FEMALES
  • KIDNEY
  • PROTEINURIA

Fabry disease: progression of nephropathy, and prevalence of cardiac and cerebrovascular events before enzyme replacement therapy

Tools:

Journal Title:

Nephrology Dialysis Transplantation

Volume:

Volume 24, Number 7

Publisher:

, Pages 2102-2111

Type of Work:

Article | Final Publisher PDF

Abstract:

Background. In Fabry disease, progressive glycolipid accumulation leads to organ damage and early demise, but the incidence of renal, cardiac and cerebrovascular events has not been well characterized.Methods. We conducted a retrospective chart review of 279 affected males and 168 females from 27 sites (USA, Canada, Europe). The pre-defined study endpoints included progression of renal, cardiac and cerebrovascular involvement andor death before the initiation of enzyme replacement therapy.Results. The mean rate of estimated glomerular filtration rate (eGFR) decline for patients was -2.93 for males, and -1.02 mlmin1.73 m2year for females. Prevalence and severity of proteinuria, baseline eGFR <60 mlmin1.73 m2and hypertension were associated with more rapid loss of eGFR. Advanced Fabry nephropathy was more prevalent and occurred earlier among males than females. Cardiac events (mainly arrhythmias), strokes and transient ischaemic attacks occurred in 49, 11, 6 of males, and in 35, 8, 4 of females, respectively. The mean age at death for 20 male patients was 49.9 years.Conclusions. Baseline proteinuria, reduced baseline eGFR, hypertension and male gender were associated with more rapid progression of Fabry nephropathy. The eGFR progression rate may increase with advancing nephropathy, and may differ between subgroups of patients with Fabry disease.

Copyright information:

© The Author [2009]. The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated.

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