NDT Advance Access originally published online on March 29, 2007
Nephrology Dialysis Transplantation 2007 22(7):1920-1925; doi:10.1093/ndt/gfm096
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Safety and pharmacokinetics of agalsidase alfa in patients with Fabry disease and end-stage renal disease
1New York University School of Medicine, New York, NY, 2Fullerton Genetics Center, Asheville, NC and 3St. Louis Children's Hospital, St. Louis, MO, USA
Correspondence and offprint requests to: Gregory M. Pastores, MD, Departments of Neurology and Pediatrics, 403 East 34th Street, New York, NY 10016, USA. Email: gregory.pastores{at}med.nyu.edu
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Abstract |
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Background. Fabry disease (FD) is caused by an X-linked deficiency in the activity of 
-galactosidase A and the resultant accumulation of globotriaosylceramide (Gb3) in multiple tissues. Nearly all classically affected males with FD experience kidney dysfunction, with progression to end-stage renal disease (ESRD) in the third decade of life or shortly thereafter.
Methods. Twenty-two FD patients (20 men and 2 women) receiving dialysis or who had a history of kidney transplantation were treated with agalsidase alfa in an open label setting using the same dosing regimen given to patients without ESRD (0.2 mg/kg every other week). Pharmacokinetics (PK) were determined during and following the initial dose, and safety was evaluated during therapy. Change in plasma Gb3 level was used as a surrogate marker of enzyme activity in vivo.
Results. A typical biphasic plasma elimination profile was seen in both dialysis and transplant patients, similar to that observed in 18 non-ESRD FD patients. Calculated PK parameters were similar to the three patient groups. In the male patients, plasma Gb3 level declined by 43% after 6 months (P < 0.001). Infusion reactions were experienced by 8 of 21 (38%) patients, but did not result in any infusions being stopped prematurely. Anti-agalsidase alfa IgG antibodies were detected in 15.8% of males and 0% female patients. No anti-agalsidase alfa IgE antibodies were detected.
Conclusions. The same dosing regimen of agalsidase alfa may be safely administered to FD patients with ESRD as given to those without ESRD.
Keywords: agalsidase alfa; dialysis; Fabry disease; kidney transplant; pharmacokinetics
Received for publication: 13.12.06
Accepted in revised form: 1. 2.07