Pathology and pathogenic pathways in fabry nephropathy

Abstract

Background: The pathophysiology of renal damage in Fabry nephropathy involves a complex biological mechanism. The intracellular deposition globotriaosylceramide (Gb3) is just the first step of the mechanism. The glycolipid deposition occurs in all renal cells (endothelial, epithelial and mesangial cells). It stimulates many biological processes, including cytokine release, epithelial-mesenchymal transdifferentiation, oxidative stress and the remodelling of vascular walls, resulting in subtle initial inflammation and eventually tissue fibrosis. It has been hypothesized that the processes activated by Gb3 deposition can subsequently progress independently of cellular deposition and that even Gb3 clearance by specific therapy cannot retard or stop these pathways.

Aim: This review aims to gather the reported evidence of these cellular alterations and the resulting histological changes. Our approach is similar to a routine study of kidney biopsy.

Results: In the first part of the review, "histology" section, we describe the structures involved (glomeruli, vessels, tubules and interstitium) from a histological point of view. While in the second part, "pathogenesis" section, we present some interpretations about the implicated pathways based on the up-to-date available evidence.

Keywords: Epithelial-mesenchymal transformation; Fabry nephropathy; Gb3/lysoGb3; Oxidative-stress; Renal fibrosis.