Fabry disease: progression of nephropathy, and prevalence of cardiac and cerebrovascular events before enzyme replacement therapy.
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 and/or 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 ml/min/1.73 m(2)/year for females. Prevalence and severity of proteinuria, baseline eGFR <60 ml/min/1.73 m(2) and 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.
Schiffmann
Raphael
R
Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke National Institutes of Health, Bethesda, MD, USA.
Warnock
David G
DG
Banikazemi
Maryam
M
Bultas
Jan
J
Linthorst
Gabor E
GE
Packman
Seymour
S
Sorensen
Sven Asger
SA
Wilcox
William R
WR
Desnick
Robert J
RJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D002561:Cerebrovascular Disorders / Q000453:epidemiology* / Q000209:etiology*; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D000795:Fabry Disease / Q000150:complications*; D005260:Female; D006331:Heart Diseases / Q000453:epidemiology* / Q000209:etiology*; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D012189:Retrospective Studies; D055815:Young Adult