Agalsidase Benefits Renal Histology in Young Patients with Fabry Disease

TLDR

The effect of early‑onset enzyme replacement therapy on renal morphologic features in Fabry disease is largely unknown. We evaluated the effect of 5 years of agalsidase alfa or beta treatment in 12 consecutive patients aged 7–33 years. Renal biopsies were obtained at baseline and after 5 years of therapy, with 7 patients also biopsied at 1 and 3 years. After 5 years, biopsies showed complete clearance of glomerular endothelial and mesangial inclusions in all patients, dose‑dependent podocyte clearance, and normalization of microalbuminuria in five patients.

Abstract

The effect of early-onset enzyme replacement therapy on renal morphologic features in Fabry disease is largely unknown. Here, we evaluated the effect of 5 years of treatment with agalsidase alfa or agalsidase beta in 12 consecutive patients age 7–33 years (median age, 16.5 years). We performed renal biopsies at baseline and after 5 years of enzyme replacement therapy; 7 patients had additional biopsies after 1 and 3 years. After a median of 65 months, biopsy findings from all patients showed total clearance of glomerular endothelial and mesangial cell inclusions, and findings from 2 patients showed complete clearance of inclusions from epithelial cells of the distal tubule. The 4 patients who received the highest dose of agalsidase exhibited substantial clearance of podocyte inclusions, and the youngest patient had nearly complete clearance of these inclusions. Linear regression analysis showed a highly significant correlation between podocyte globotriaocylceramide clearance and cumulative agalsidase dose (r=0.804; P=0.002). Microalbuminuria normalized in five patients. In summary, long-term enzyme replacement therapy in young patients can result in complete globotriaocylceramide clearance of mesangial and glomerular endothelial cells across all dosage regimens, and clearance of podocyte inclusions is dose-dependent.