Long-term enzyme replacement therapy is associated with reduced proteinuria and preserved proximal tubular function in women with Fabry disease

Background Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the GLA gene. Deficiency of α-galactosidase A (α-Gal A) causes intracellular accumulations of globotriaosylceramide (GL-3) and related glycosphingolipids in all organs, including the kidney, often leading to end-stage renal failure. In women with Fabry disease, accumulation of GL-3 in the glomerular podocytes and other renal cells induces progressive, proteinuric nephropathy, but not as severe as in men. Enzyme replacement therapy (ERT) with recombinant α-Gal A reduces cellular GL-3 deposits in podocytes and tubular epithelial cells. We have previously shown that α-Gal A is delivered to these cells by different pathways involving different receptors. This study investigated the long-term changes in albuminuria, estimated glomerular filtration rate (eGFR) and urinary markers of both glomerular and tubular dysfunction in women with Fabry disease treated with ERT. Methods A retrospective, single centre, cohort study evaluated the long-term association between ERT, albuminuria and eGFR in 13 women with Fabry disease and mild renal involvement. In particular, we analysed the changes in the proteinuric profile, including the glomerular marker IgG, the tubular markers α1-microglobulin and retinol-binding protein (RBP), and the shared tubular and glomerular markers albumin and transferrin. Results ERT was associated with a significant reduction in albuminuria and a relatively stable eGFR. The decrease in albuminuria was paralleled by a decrease in both glomerular and tubular urine protein markers. Conclusions The data indicate that long-term ERT is associated with a reduction in albuminuria and glomerular and tubular urinary protein markers in women with Fabry disease and mild renal manifestation