University of Bristol, Academic Renal Unit, Learning and Research, Southmead Hospital, Bristol BS10 5NB, UK.
Nat Rev Nephrol. 2013 Dec;9(12):717-25. doi: 10.1038/nrneph.2013.197. Epub 2013 Oct 1.
The unique permeability characteristics of the glomerular capillary wall depend on its three-layer structure, consisting of endothelial cells, the basement membrane and podocytes. These components form the glomerular filtration barrier (GFB). That albuminuria may occur in the absence of changes in podocyte foot processes suggests that GFB components other than podocytes have essential roles in albumin handling. The endothelium forms the first part of the GFB and is characterized by fenestrations-transcellular holes that are filled with endothelial glycocalyx, a hydrated mesh principally comprised of proteoglycans. The glycocalyx and adsorbed plasma constituents form the endothelial surface layer (ESL). Human and animal studies have shown that the glomerular ESL restricts macromolecule passage and ensures that plasma albumin is largely excluded from the GFB. The glomerular endothelium is also likely to indirectly influence glomerular albumin handling by modifying podocyte behaviour. These modifications may occur physiologically through soluble mediators and/or pathologically through increased exposure of podocytes to plasma components as a consequence of ESL dysfunction. The importance of the glomerular endothelium and ESL in albumin handling also sheds light on the relationship between albuminuria and vascular disease. The therapeutic potential that this relationship offers will become evident with better understanding of the structure, composition and regulation of the glycocalyx.
肾小球毛细血管壁的独特通透性特征取决于其三层结构，包括内皮细胞、基底膜和足细胞。这些成分构成了肾小球滤过屏障（GFB）。即使足细胞的足突没有发生变化也会出现白蛋白尿，这表明除了足细胞以外，GFB 的其他成分在白蛋白处理中也具有重要作用。内皮细胞构成了 GFB 的第一部分，其特征是有孔——跨细胞孔，这些孔充满了内皮糖萼，这是一个主要由蛋白聚糖组成的水合网格。糖萼和吸附的血浆成分构成了内皮表面层（ESL）。人体和动物研究表明，肾小球 ESL 限制了大分子的通过，并确保了血浆白蛋白大部分被排除在 GFB 之外。肾小球内皮细胞也可能通过改变足细胞的行为间接影响肾小球白蛋白的处理。这些改变可能通过可溶性介质在生理上发生，或者通过 ESL 功能障碍导致足细胞暴露于更多的血浆成分而在病理上发生。肾小球内皮细胞和 ESL 在白蛋白处理中的重要性也揭示了白蛋白尿与血管疾病之间的关系。随着对糖萼的结构、组成和调节的更好理解，这种关系提供的治疗潜力将变得明显。
