What are the characteristic kidney biopsy findings in Fabry disease?
In patients with the Type 1 Classic Phenotype, chronic kidney disease is due to GL-3 accumulation primarily in the microvascular endothelium and podocytes. The typical concentric lamellar lysosomal inclusions, which appear like “onion skin” or “zebra bodies,” are best seen by electron microscopy. They also can be seen histologically as foamy periodic acid–Schiff positive inclusions on frozen sections. The podocytopathy causes proteinuria. To a lesser extent, and in later stages of disease, the proximal tubules, histiocytes, mesangial, and interstitial cells all develop glycolipid accumulation. Lipid-laden distal tubular epithelial cells and podocytes desquamate and can be detected by urine microscopy. Nonspecific pathologic changes such as arteriolar sclerosis, glomerular atrophy and fibrosis, tubular atrophy, and diffuse fibrosis can be seen in the later stages of disease. Biopsies early in the disease course will show histologically the foamy inclusions in most cell types, and early podocyte effacement is an important sign of kidney disease requiring treatment. The histology of the ESKD is not diagnostic, and electron microscopy is needed to visualize the characteristic lamellar cytoplasmic inclusions in the kidney lysosomes.
Of note, kidney glycosphingolipid accumulation in Type 2 Later-Onset males occurs primarily in the podocytes with little involvement of the glomerular vascular endothelial, interstitial, or mesangial cells.
