Fabry disease is a rare lysosomal storage disorder caused by mutations in the GLA gene, which, without treatment, can cause significant renal dysfunction. We evaluated the effects of enzyme replacement therapy with agalsidase alfa on renal decline in patients with Fabry disease using data from the Fabry Outcome Survey (FOS) registry. Male patients with Fabry disease aged >16 years at agalsidase alfa start were stratified by low (≤0.5 g/24 h) or high (>0.5 g/24 h) baseline proteinuria and by ‘classic’ or ‘non-classic’ phenotype. Overall, 193 male patients with low (n = 135) or high (n = 58) baseline proteinuria were evaluated. Compared with patients with low baseline proteinuria, those with high baseline proteinuria had a lower mean ± standard deviation baseline eGFR (89.1 ± 26.2 vs. 106.6 ± 21.8 mL/min/1.73 m2) and faster mean ± standard error eGFR decline (−3.62 ± 0.42 vs. −1.61 ± 0.28 mL/min/1.73 m2 per year; p < 0.0001). Patients with classic Fabry disease had similar rates of eGFR decline irrespective of baseline proteinuria; only one patient with non-classic Fabry disease had high baseline proteinuria, preventing meaningful comparisons between groups. In this analysis, baseline proteinuria significantly impacted the rate of eGFR decline in the overall population, suggesting that early treatment with good proteinuria control may be associated with renoprotective effects.

2nd Department of Medicine Department of Cardiovascular Medicine 1st Faculty of Medicine Charles University and General University Hospital 12808 Prague Czech Republic

Center of Internal Medicine Department of Nephrology and Rheumatology Nephrologicum Markgräflerland MVZ 79379 Müllheim Germany

Department of Internal Medicine Slovenj Gradec General Hospital 2380 Slovenj Gradec Slovenia

Department of Medicine Dalhousie University Halifax NS B3H 4R2 Canada

Department of Medicine University of Melbourne Parkville VIC 3010 Australia

Department of Nephrology Royal Melbourne Hospital Parkville VIC 3050 Australia

Faculty of Medicine Campus Bellvitge University of Barcelona L'Hospitalet de Llobregat 08907 Barcelona Spain

Institut d'Investigació Biomèdica de Bellvitge L'Hospitalet de Llobregat 08908 Barcelona Spain

Nephrology and Dialysis Unit Belcolle Hospital 01100 Viterbo Italy

Takeda Pharmaceuticals International AG 8152 Zurich Switzerland

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