Enzyme replacement therapy administered during hemodialysis in patients with Fabry disease

Background. Enzyme replacement treatment with recombinant human alpha-galactosidase A (r-halphaGalA) is now available for patients with Fabry disease, many of whom are on maintenance hemodialysis. Because r-halphaGalA must be infused over several hours, administering the enzyme during dialysis would save a day of treatment for patients receiving both therapies. However, these procedures have never been combined due to concerns about possible loss of enzyme in the dialysate. Methods. Ten Fabry patients received r-halphaGalA (1 mg/kg body weight continuously infused over 4 hours) during dialysis and separately in the interval between dialysis treatments. Plasma activity of r-halphaGalA was measured at baseline and then every hour for both procedures. In two patients, a third r-halphaGalA infusion during dialysis with a high-flux membrane was followed. Results. The rise in plasma concentrations of r-halphaGalA during infusion and the steady-state levels reached were comparable for enzyme administrations with or without dialysis. The trend for the somewhat higher activities during hemodialysis was explained by volume contraction due to ultrafiltration. With the use of a high-flux dialyzer, the plasma r-halphaGalA activities were identical to those that were observed during low-flux dialysis. Conclusions. Administration of r-halphaGalA during hemodialysis is not associated with a reduced activity of r-halphaGalA therapy in patients with Fabry disease. Replacement therapy with r-halphaGalA may therefore be performed during hemodialysis without apparent loss of enzyme into the dialysate.