title: Clinical benefit of enzyme replacement therapy in Fabry disease.
abstract: Enzyme replacement therapy (ERT) with recombinant human alpha-galactosidase A (r-halphaGalA) enhances microvascular globotriaosylceramide clearance and improves clinical symptoms in patients with Fabry disease. We evaluated whether these effects are translated into a long-term benefit of kidney and heart function. We did a single center, prospective, open label study in 26 patients with Fabry disease (one early death, follow-up in 25 patients). r-Alpha-GalA was administered in a dosage of 1 mg/kg body weight every second week. The effect of therapy on clinical end points (death, cardiac and cerebrovascular event, renal failure), cardiac and renal function monitored by Doppler echocardiography, 99Tc-GFR, and proteinuria was investigated. After a mean treatment time of 23 +/- 8 months, nine patients experienced 12 end points, including two deaths. All end points occurred in patients with impaired renal function (n = 16; GFR 71 +/- 17 ml/min/1.73 m2). Despite ERT, renal function deteriorated to 60 +/- 23 ml/min/1.73 m2 (P = 0.04) and left ventricular posterior wall thickness (PWT) did not change (14.0 +/- 2.1 vs 13.4 +/- 2.3 mm). In contrast, patients without impairment of renal function (n = 9) had a more favorable outcome (no clinical events; GFR 115 +/- 18 vs 102 +/- 14 ml/min/1.73 m2, NS; PWT 11.7 +/- 1 and 10.7+/-0.7 mm, P = 0.04). Proteinuria remained unchanged (1.34 +/- 0.94 vs 1.01 +/- 0.97 g/day, n = 10). Patients with impaired renal function have a less favorable outcome and may develop cardiovascular and renal end points despite ERT.
authors.affiliation: Department of Medicine, Division of Nephrology, University Hospital, Würzburg, Germany. breunig_f@klinik.uni-wuerzburg.de
authors.forename: F
authors.initials: F
authors.lastname: Breunig
authors.forename: F
authors.initials: F
authors.lastname: Weidemann
authors.forename: J
authors.initials: J
authors.lastname: Strotmann
authors.forename: A
authors.initials: A
authors.lastname: Knoll
authors.forename: C
authors.initials: C
authors.lastname: Wanner
mesh_terms: D000328:Adult; D004452:Echocardiography; D000795:Fabry Disease / Q000628:therapy*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use*; D000519:alpha-Galactosidase / Q000627:therapeutic use*
chemical_list: D011994:Recombinant Proteins; D000519:alpha-Galactosidase