Clinical benefit of enzyme replacement therapy in Fabry disease

Enzyme replacement therapy (ERT) with recombinant human α-galactosidase A (r-hαGalA) 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-α-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.