Rozenfeld Paula, Feriozzi Sandro, Braun Fabian
Instituto de Estudios Inmunológicos y Fisiopatológicos (IIFP), UNLP, CONICET, Asociado CIC PBA, Facultad de Ciencias Exactas, La Plata, Argentina.
Nephrology and Dialysis Unit, Belcolle Hospital, Viterbo, Italy.
Front Cardiovasc Med. 2024 Apr 5;11:1386042. doi: 10.3389/fcvm.2024.1386042. eCollection 2024.
The pathophysiology of Fabry nephropathy (FN) is induced by galactosidase A deficiency with a chronic exposure of glycolipids to every lineage of renal cells. Tissue damage is attributed to the activation of molecular pathways, resulting in tissue fibrosis and chronic kidney disease. Podocytes have been the primary focus in clinical pathophysiological research because of the striking accumulation of large glycolipid deposits observable in histology. Yet, the tubular interstitium makes up a large portion of the whole organ, and therefore, its role must be further considered in pathogenic processes. In this review, we would like to propose Fabry tubulopathy and its ensuing functional effects as the first pathological signs and contributing factors to the development of FN. We will summarize and discuss the current literature regarding the role of tubular cells in Fabry kidney pathophysiology. Starting from clinical and histological evidence, we will highlight the data from animal models and cell cultures outlining the pathophysiological pathways associated with tubular interstitial injury causing renal fibrosis in Fabry nephropathy.
法布里肾病（FN）的病理生理学是由α-半乳糖苷酶A缺乏引起的，糖脂长期暴露于肾细胞的各个谱系。组织损伤归因于分子途径的激活，导致组织纤维化和慢性肾病。由于在组织学上可观察到大量糖脂沉积物的显著积累，足细胞一直是临床病理生理学研究的主要焦点。然而，肾小管间质占整个器官的很大一部分，因此，其在致病过程中的作用必须进一步加以考虑。在本综述中，我们提出法布里肾小管病及其随后的功能影响作为FN发展的首个病理体征和促成因素。我们将总结并讨论目前关于肾小管细胞在法布里肾病病理生理学中作用的文献。从临床和组织学证据出发，我们将重点介绍动物模型和细胞培养的数据，概述与导致法布里肾病肾纤维化的肾小管间质损伤相关的病理生理途径。
