Enzyme replacement therapy with agalsidase beta in kidney transplant patients with Fabry disease: a pilot study.
BACKGROUND
We sought to assess the safety and efficacy of enzyme replacement therapy (ERT) with recombinant human-alpha-galactosidase A (rh-alpha-Gal A) in kidney transplant recipients with Fabry disease, a previously unstudied population.


METHODS
Three male kidney transplant recipients with biochemically, genetically, and histologically confirmed Fabry disease and documented Fabry myocardiopathy received the rh-alpha-Gal A, agalsidase beta, 1 mg/kg of body weight every 2 weeks by intravenous infusion and were monitored biochemically, clinically, and electrocardiographically and echocardiographically for 18 months.


RESULTS
Patients showed biochemical, clinical/functional, and morphologic response to ERT. Plasma globotriaosylceramide decreased 23% to 50%. Extremity pain resolved within 2 months in the patient with this manifestation. On echocardiography, left ventricular mass, end diastolic diameter (EDD), and cardiac contractility, shown by ejection fraction (EF), improved in 2 of the 3 patients receiving essentially all planned infusions. EDD and EF remained basically stable, but cardiac morphologic abnormalities progressed in the other patient, who had a 5-month interruption in ERT after the initial month. Mild mitral insufficiency persisted in all patients, as did atrial fibrillation in the affected individual. After a combined total of 116 infusions, no treatment-related adverse event, intolerance, or seroconversion was seen. Renal function remained stable and the immunosuppression regimen unchanged in all patients.


CONCLUSIONS
Our pilot study provides preliminary evidence that ERT with agalsidase beta, 1 mg/kg every 2 weeks, is safe and often effective against extra-renal manifestations in kidney transplant patients with Fabry disease. Studies with longer courses of this and higher doses of ERT are merited in this population.
Mignani
Renzo
R
Department of Nephrology and Dialysis, Infermi Hospital, Rimini, Italy. rmignani@auslrn.net
Panichi
Vincenzo
V
Giudicissi
Antonio
A
Taccola
Daniele
D
Boscaro
Francesca
F
Feletti
Carlo
C
Moneti
Gloriano
G
Cagnoli
Leonardo
L
D000328:Adult; D001281:Atrial Fibrillation / Q000209:etiology / Q000503:physiopathology; D004452:Echocardiography; D004562:Electrocardiography; D005121:Extremities; D000795:Fabry Disease / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000601:surgery*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D007527:Isoenzymes / Q000627:therapeutic use*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D008944:Mitral Valve Insufficiency / Q000209:etiology / Q000503:physiopathology; D010146:Pain / Q000503:physiopathology; D010865:Pilot Projects; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome; D014281:Trihexosylceramides / Q000097:blood; D000519:alpha-Galactosidase / Q000627:therapeutic use*
D007527:Isoenzymes; D011994:Recombinant Proteins; D014281:Trihexosylceramides; C018549:globotriaosylceramide; D000519:alpha-Galactosidase; C459420:agalsidase beta