Introduction and Aims: Fabry disease is an X-linked lysosomal storage
disorder caused by absence or deficient activity of the lysosomal enzyme
alpha-galactosidase A. Renal manifestations occur early in life in a significant
proportion of children, in many women and in almost all men with
Fabry disease. These manifestations ultimately progress to end-stage renal
disease in nearly all males and in some female patients. Data on kidney
transplantation in patients with Fabry disease who are receiving enzyme
replacement therapy (ERT), however, are scarce.
Methods: We examined the clinical characteristics of kidney transplant
recipients (KTRs) in the Fabry Outcome Survey (FOS) - a European
database of patients with Fabry disease that was established to monitor the
safety and outcome of ERT.
Results: Of the 752 patients enrolled in FOS up to October 2005, 34 (4.5%)
were reported to be KTRs. The mean age of these 32 male and 2 female
patients was 45 ± 9 years, the median time since the transplant was 9 years,
the median estimated glomerular filtration rate (eGFR) was 46 mL/min/1.73
m2 and the median level of proteinuria was 180 mg/24 hours. ERT was well
tolerated, with mild infusion-related reactions reported in only one patient.
Amongst these patients, 53% were reported to have hypertension, 71% left
ventricular hypertrophy, 27% cardiac valve disease and 27% arrhythmia. A
total of 23 (68%) of the patients (1 female, 22 males) were receiving ERT
with agalsidase alfa (Replagal; Shire Human Genetic Therapies, UK), with
a median duration of treatment of 2.5 years. There were no differences in
age or time since transplantation between treated and untreated patients.
The median eGFRs were 46 and 49 mL/min/1.73 m2 and the median levels
of proteinuria were 200 and 160 mg/24 hours, respectively.
Conclusions: KTRs represent a significant minority of individuals enrolled
in a large international registry of patients with Fabry disease (FOS).
Approximately two-thirds of KTRs with Fabry disease enrolled in FOS
receive ERT with agalsidase alfa, which is well tolerated. Comparison of
treated and untreated patients has the potential to examine effects of ERT
on the progression of renal and cardiovascular disease.