Safety and efficacy of enzyme replacement therapy in the nephropathy of Fabry disease

Fernando C Fervenza¹, Roser Torra², David G Warnock³

¹Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, MN, USA; ²Department of Nephrology, Fundació Puigvert, Barcelona, Spain; ³Division of Nephrology, University of Alabama at Birmingham, Birmingham, AL, USA

Abstract: Kidney involvement with progressive loss of kidney function (Fabry nephropathy) is an important complication of Fabry disease, an X-linked lysosomal storage disorder arising from deficiency of α-galactosidase activity. Clinical trials have shown that enzyme replacement therapy (ERT) with recombinant human α-galactosidase clears globotriaosylceramide from kidney cells, and can stabilize kidney function in patients with mild to moderate Fabry nephropathy. Recent trials show that patients with more advanced Fabry nephropathy and overt proteinuria do not respond as well to ERT alone, but can benefit from anti-proteinuric therapy given in conjunction with ERT. This review focuses on the use of enzyme replacement therapy with agalsidase-alfa and agalsidase-beta in adults with Fabry nephropathy. The current results are reviewed and evaluated. The issues of dosing of enzyme replacement therapy, the use of adjunctive agents to control urinary protein excretion, and the individual factors that affect disease severity are reviewed.

Keywords: agalsidase, enzyme replacement therapy, Fabry nephropathy, anti-proteinuric therapy