Jarad George, Miner Jeffrey H
Renal Division, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Curr Opin Nephrol Hypertens. 2009 May;18(3):226-32. doi: 10.1097/mnh.0b013e3283296044.
The nephrology community lacks a unified view of protein sieving through the glomerular capillary wall. The glomerular capillary wall consists of three distinct but closely interacting layers: the fenestrated endothelium, with its glycocalyx; the podocytes, with their interdigitated foot processes and slit diaphragms; and the intervening glomerular basement membrane. Proteinuria is associated with abnormalities in any one layer, suggesting that each contributes to the glomerular filtration barrier (GFB). Proteinuria can also be induced in the context of a normal glomerular capillary wall. Here, we review some classic studies as well as some newer concepts and present competing hypotheses about the GFB.
Two almost forgotten concepts have recently emerged. One group has challenged the exquisite selectivity of the GFB to albumin and suggested that proteinuria is the result of abnormal tubular uptake. There has also been a reemphasis on diffusion through the glomerular basement membrane as the driving force behind macromolecular filtration. New evidence suggests that the endothelial glycocalyx is an important charge-selective barrier.
We suggest viewing the GFB as a dynamic rather than as a rigid barrier, requiring three healthy layers and a hemodynamic steady state. Multiple challenges to studying the endothelium, the tubular handling of albumin, and the role of hemodynamic forces will require new tools, new hypotheses, and open minds.
肾脏病学界对蛋白质通过肾小球毛细血管壁的筛选缺乏统一的认识。肾小球毛细血管壁由三个不同但紧密相互作用的层组成：有糖萼的有孔内皮；有指状足突和裂孔隔膜的足细胞；以及中间的肾小球基底膜。蛋白尿与任何一层的异常有关，这表明每一层都对肾小球滤过屏障（GFB）有贡献。蛋白尿也可在正常肾小球毛细血管壁的情况下诱发。在此，我们回顾一些经典研究以及一些新的概念，并提出关于GFB的相互竞争的假说。
最近出现了两个几乎被遗忘的概念。一组人对GFB对白蛋白的精细选择性提出了质疑，并认为蛋白尿是肾小管摄取异常的结果。还再次强调通过肾小球基底膜的扩散是大分子滤过背后的驱动力。新证据表明内皮糖萼是一个重要的电荷选择性屏障。
我们建议将GFB视为一个动态而非刚性的屏障，需要三个健康的层和血流动力学稳定状态。研究内皮、白蛋白的肾小管处理以及血流动力学力量的作用面临的多重挑战将需要新的工具、新的假说和开放的思维。
