The effectiveness of long-term agalsidase alfa therapy in the treatment of Fabry nephropathy.

Background And Objectives: Fabry disease is a rare X-linked disease with multisystemic manifestations. This study investigated the effectiveness of long-term enzyme replacement therapy with agalsidase alfa in Fabry nephropathy treatment.

Design, Setting, Participants, & Measurements: In this observational study, data on patients receiving agalsidase alfa (0.2 mg/kg every other week) were extracted from the Fabry Outcome Survey, an international registry of patients with Fabry disease. Serum creatinine and estimated GFR (eGFR) at baseline and after ≥5 years of treatment were assessed; 24-hour urinary protein excretion and BP measurements were also reviewed. The eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration formula. Patients with an eGFR <30 ml/min per 1.73 m(2) were excluded.

Results: Renal function was assessed in 208 patients (mean enzyme replacement therapy, 7.4 years; range, 5.0-11.2 years). Mean yearly change in eGFR was -2.2 ml/min per 1.73 m(2) in men and -0.7 ml/min per 1.73 m(2) in women (95% confidence limits, -2.8; -1.7 and -1.4; 0.0, respectively). Patients with 24-hour protein excretion >1 g/24 h had poorer renal function at baseline and follow-up compared with patients with protein excretion of 500-1000 mg/24 h or with proteinuria <500 mg/24 h. Renal function was worse in patients with baseline arterial hypertension, and there was a more rapid yearly decline compared with normotensive patients.

Conclusions: This study suggests that long-term agalsidase alfa therapy is able to stabilize the rate of Fabry nephropathy progression in women and is associated with a mild to moderate decline of renal function in men.