Renal Manifestations of Fabry Disease: A Narrative Review

Abstract

Purpose of review: In this narrative review, we describe general aspects, histological alterations, treatment, and implications of Fabry disease (FD) nephropathy. This information should be used to guide physicians and patients in a shared decision-making process.

Source of information: Original peer-reviewed articles, review articles, and opinion pieces were identified from PubMed and Google Scholar databases. Only sources in English were accessed.

Methods: We performed a focused narrative review assessing the main aspects of FD nephropathy. The literature was critically analyzed from a theoretical and contextual perspective, and thematic analysis was performed.

Key findings: FD nephropathy is related to the progressive accumulation of GL3, which occurs in all types of renal cells. It is more prominent in podocytes, which seem to play an important role in the pathogenesis of this nephropathy. A precise detection of renal disorders is of fundamental importance because the specific treatment of FD is usually delayed, making reversibility unlikely and leading to a worse prognosis.

Limitations: As no formal tool was applied to assess the quality of the included studies, selection bias may have occurred. Nonetheless, we have attempted to provide a comprehensive review on the topic using current studies from experts in FD and extensive review of the literature.

Keywords: Fabry; chronic kidney disease; end-stage renal disease; kidney disease; renal failure.

Figure 1.

Kidney biopsy specimen under light microscopy (A-E—embedded in paraffin): The vacuoles seen in the cytoplasm of different cells: especially podocytes (P) in the glomerulus (G), distal tubular cells (T), and Henle loops (HL). (A) Hematoxylin and eosin (magnification: 20× objective; 2.0× optovar). (B-E) Masson’s trichrome (magnification: 160×). (F) Yellowish green natural fluorescence of GL3 in the glomerular and tubular cells (arrows) in frozen section under fluorescence microscopy (magnification: 40× objective; 1.25× optovar).

Figure 2.

Kidney biopsy specimen under light microscopy—osmicated, epoxy-embedded tissue, stained with toluidine blue. There are GL3 deposits stained in dense, dark blue granules in the cytoplasm of different cells: especially in enlarged podocytes in glomerulus (G) and parietal epithelial cells (Bowman capsule; arrows), tubular cells (T), endothelial cells and smooth muscle cells in arteriole (A), and in interlobular arteria (IA). There is segmental sclerosis (SS) in glomerulus (A-D, magnification: 20× objective; 2.0× optovar).

Figure 3.

Kidney biopsy specimen under electron microscopy: (A-C) Glomerulus with electron-dense GL3 deposits in endothelial cells (EC), mesangial cells (MC), parietal epithelial cells (PEC), and podocytes (P), with effacement foot process (arrow). (D) In high magnification, GL3 deposits consist of electron-dense multilamellated concentric layers, with periodicity 3.5 to 5 nm (arrow). Original magnification: (A) = 4.400×, (B) = 3.000×, (C) = 7.000×, and (D) = 250.000×.

Figure 4.

Kidney biopsy specimen under electron microscopy with electron-dense GL3 deposits in lysosomes in different cells: (A) arteriole in endothelial cells (EC) and smooth muscle cells (SMC); (B) distal tubule (DT) and in endothelial cells (EC) of peritubular capillary (PTC); (C) proximal tubule (PT); and (D) cells in the interstitial compartment. Original magnification: (A-D) = 3.000×. Note. RBC = red blood cell; BM = basal membrane.