Nephrology and Dialysis Unit, Belcolle Hospital, Via Sammartinese, snc, 01100, Viterbo, Italy.
Facultad de Ciencias Exactas, Departamento de Ciencias Biológicas, Asociado CIC PBA, Instituto de Estudios Inmunológicos y Fisiopatológicos [IIFP], UNLP, CONICET, La Plata, Argentina.
Clin Exp Nephrol. 2021 Sep;25(9):925-934. doi: 10.1007/s10157-021-02058-z. Epub 2021 Mar 26.
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.
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.
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.
法布里肾病肾损伤的病理生理学涉及复杂的生物学机制。细胞内糖脂基三己糖苷（Gb3）的沉积只是该机制的第一步。糖脂沉积发生在所有的肾细胞（内皮细胞、上皮细胞和系膜细胞）中。它刺激了许多生物学过程，包括细胞因子释放、上皮-间充质转化、氧化应激和血管壁重塑，导致细微的初始炎症，最终导致组织纤维化。有人假设，Gb3 沉积激活的过程可以独立于细胞沉积而进一步发展，即使通过特定的治疗清除 Gb3 也不能延缓或阻止这些途径。
本综述旨在收集关于这些细胞改变和由此产生的组织学变化的报告证据。我们的方法类似于对肾脏活检的常规研究。
在综述的第一部分，即“组织学”部分，我们从组织学的角度描述了涉及的结构（肾小球、血管、肾小管和间质）。而在第二部分，即“发病机制”部分，我们根据最新的现有证据对涉及的途径提出了一些解释。
