Biography
Biography: Abdulhafid Shebani
Abstract
Classic Fabry disease, an X-linked nephropathy resulting from deficiency of lysosomal α-galacto sidase A, typically leads to renal failure, cardiac disease, and cerebrovascular disease by the third to fifth decades of life.
Nephropathy is one of the major complications of Fabry disease. Kidney biopsies show globotriaosylceramide (GL-3) accumulation in tubular epithelial cells, glomerular and endothelial cells, and vascular smooth muscle cells. With time, progressive GL-3 accumulation leads to microvascular dysfunction, occlusion, and ischemia, with subsequent development of tubular atrophy, segmental and global sclerosis, and interstitial fibrosis. Affected male individuals classically develop ESRD by the fourth decade of life.
Increasing evidence emphasizes the importance of early treatment of Fabry disease, before renal pathology becomes irreversible. The recent randomized, double-blind, placebo-controlled clinical trial of Enzyme replacement therapy (ERT) in Fabry patients with mild to moderate renal failure found that risk rates for renal, cardiac, and cerebrovascular events, together and individually, were significantly decreased in patients on ERT after the pre specified adjustment for baseline proteinuria, particularly in patients with milder renal disease.
The goal for treatment of Fabry nephropathy is reduction in the rate of loss of GFR to #21.0 ml/min per 1.73 m2/yr. Measuring proteinuria and urinary sodium excretion are important first steps. If proteinuria is not controlled, then antiproteinuric dosing increases are recommended, It may be necessary to reduce the dosage of other antihypertensive agents (e.g., b blockers, diuretics, calcium channel blockers) so that ACEI or ARB dosing can be increased.
Enzyme replacement therapy (ERT) with re combinant α-galactosidase A is safe and effective in Fabry disease, reversing pathologic glycosphingolipid deposits in renal vascular endothelial, interstitial, and mesangialcells, and reducing accumulations of these deposits in the podocytes and tubular epithelial cells.