Fabry Disease Chronic Kidney Disease

Fabry disease (FD) arises from an X-linked defect in lipid storage, whereby deficient or absent lysosomal α-galactosidase A (α-gal A) activity leads to systemic deposition of glycosphingolipids, mainly globotriaosylceramide (known as Gb3 or GL3). Deposition mainly affects the cardiovascular, renal, and neurologic systems, but can occur in all organs, and despite specific enzyme replacement therapy (ERT) with human recombinant α-galactosidase, kidney disease is progressive.1,2 Accordingly, FD is considered a genetic risk factor for kidney disease, cardiomyopathy, stroke, and early death.3 Kidney disease is a hallmark feature in male patients, with microalbuminuria and proteinuria as the initial presentation.4 The etiology of FD nephropathy is not completely understood, but vascular, glomerular, and tubular changes are probably all implicated early on in the disease; these changes have been noted in children, even in those who have only scant microalbuminuria or normoalbuminuria. For this reason, the role of podocyturia as both a biomarker and an early treatment target in preventing kidney damage is gaining prominence.4-6