Enzyme replacement therapy with agalsidase beta in kidney transplant patients with Fabry disease: a pilot study.

Abstract

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.

CONCLUSION:

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.

• Authors: Renzo Mignani, Vincenzo Panichi, Antonio Giudicissi, Daniele Taccola, Francesca Boscaro, Carlo Feletti, Gloriano Moneti, Leonardo Cagnoli
• Journal: Kidney international (Kidney Int) Vol. 65 Issue 4 Pg. 1381-5 (Apr 2004) ISSN: 0085-2538 [Print] United States
• PMID: 15086478 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Isoenzymes
• Recombinant Proteins
• Trihexosylceramides
• globotriaosylceramide
• alpha-Galactosidase
• agalsidase beta

Topics

• Adult
• Atrial Fibrillation (etiology, physiopathology)
• Echocardiography
• Electrocardiography
• Extremities
• Fabry Disease (complications, diagnosis, drug therapy, surgery)
• Heart (drug effects, physiopathology)
• Humans
• Isoenzymes (therapeutic use)
• Kidney Transplantation
• Male
• Middle Aged
• Mitral Valve Insufficiency (etiology, physiopathology)
• Pain (physiopathology)
• Pilot Projects
• Recombinant Proteins (therapeutic use)
• Treatment Outcome
• Trihexosylceramides (blood)
• alpha-Galactosidase (therapeutic use)