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

• Type of Material: Article
• Authors: Raphael Schiffmann, National Institute of Neurological Disorders and Stroke National Institutes of Health; David G. Warnock, University of Alabama at Birmingham; Maryam Banikazemi, Mount Sinai School of Medicine; Jan Bultas, Charles University Hospital Plzeň; Gabor E. Linthorst, University of Amsterdam; Seymour Packman, University of California San Francisco; Sven Asger Sorensen, University of Copenhagen; William R. Wilcox, Emory University; Robert J. Desnick, Mount Sinai School of Medicine
• Language: English
• Date: 2009-07-01
• Publisher: Oxford University Press (OUP): Policy B - Oxford Open Option B
• Publication Version: Final Published Version
• Copyright Statement: © 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.
• Final Published Version (URL): http://dx.doi.org/10.1093/ndt/gfp031
• Title of Journal or Parent Work: Nephrology Dialysis Transplantation
• ISSN: 0931-0509
• Volume: 24
• Issue: 7
• Start Page: 2102
• End Page: 2111
• Grant/Funding Information: 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: GLOMERULAR-FILTRATION-RATE; CONTROLLED TRIAL; Fabry disease; albuminuria; Life Sciences & Biomedicine; proteinuria; nephropathy; FEMALES; RENAL-FUNCTION; ALPHA-GALACTOSIDASE; KIDNEY; stroke; CLINICAL-MANIFESTATIONS; PROTEINURIA; Urology & Nephrology; AGALSIDASE-BETA THERAPY; Transplantation; Science & Technology; arrhythmia; OUTCOME SURVEY
• Research Categories: Biology, Genetics; Chemistry, Biochemistry

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.