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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 manifestations.

Background: Epirubicin is a potent and widely used citotoxic drug, but its application is often limited by the cumulative dose-dependent cardiotoxicity. LV ejection fraction (EF) and fractional shortening (FS) are the most commonly used indices to demonstrate cardiac dysfunction. Since normal EF or FS can mask significant LV impairment, we hypothesized that LV systolic torsion and deformation represent better markers of epirubicin-induced subclinical cardiac dysfunction. Methods: 40 women with breast cancer (58+9 years), without known associated cardiac disease, scheduled to be treated with epirubicin-based chemotherapy, were assessed at baseline, and after 1 and 6 cycles of epirubicin (cumulative dose of 293+15 g/m2). Conventional echocardiography was used to assess LV geometry, EF and FS. 2D speckle tracking imaging was used to measure LV systolic rotation parameters: peak apical rotation (RotA), peak basal rotation (RotB), LV twist (LVT) (as the difference in LV rotation between apical and basal planes), and twist rate (LVTR); and also LV systolic deformation indices: radial strain (rS) and strain rate (rSR), and longitudinal strain (LS) and strain rate (LSR). Results: No changes in LV dimensions, EF, and FS were observed during follow-up. However, there were significant reductions in RotA, and consequently in LVT and LVTR, with no changes in RotB; and also a significant decrease of LV radial and longitudinal deformation found after the first cycle of epirubicin and persistent after the sixth cycle (see table). Univariate analysis showed that epirubicin cumulative dose was directly correlated with longitudinal strain and LV twist reduction after 6 months of treatment (r=0.59 and r=0.79; both p,0.01). Conclusion: LV torsion and deformation parameters, assessed by 2D speckle tracking imaging, detect subclinical LV dysfunction and, therefore, can be used to monitor epirubicin-induced cardiac dysfunction.