How does Proteinuria Come into Being?

As we know, proteinuria is the main characteristic symptoms of chronic kidney disease. The reason why protein in urine comes into being is closely connected with renal glomerular filtration function. The renal glomerular blood vessels can be divided into three layers: from inner side to outer side, endothelium, basilar membrane layer and epithelial layers. In all these three layers, there are different sizes of filtration pores and negative charges. So the barrier function of renal glomerular blood vessels can be divided into 2 kinds: mechanical barrier- filtration pores- negative charges.
1. mechanical barrier- filtration pores
The mechanical barrier can be divided into three layers.
Inner layer is composed of blood capillaries of endothelial cells. In the endothelial cells, there are many ostiole, the diameter of which is 50-100nm and is called fenestration. Water, all kinds of solute and Macromolecular proteins can go through it freely. But,blood cells can be blocked, which can play roles as the barrier of blood cells.
The middle layer is the basement-membrane, which shows structure of fibre net. Bigger molecules such as protein can not pass through basement-membrane. The basement-membrane is the main barrier which prevent macro-molecules from filtration.
The outer layer is the epithelial cell. Epithelial cells have foot process, and between the foot process, there is fracture. In the fracture, there is a filtration slit membrane. On the membrane, there are holes whose diameter is as long as 4 to 14 nm. It is the last barrier. Generally speaking, the substances whose diameter is less than 1.8 nm can be filtrated. Those whose diameter is more than 3.6 nm can not pass.
2. charge barrier-negative charge
All layers of filtration contain many substances which carry negative charge. So the permeability of filtration membrane is up to the discharges of filtrated substances. Substances which carry negative discharge repel plasma protein, which carry negative discharge, and stop them from filtration. Although the diameter of plasma protein is 3.5nm, because it carries negative charges, it is hard to pass through filtration membrane. When all the pathological damages happen in kidney, which includes primary one and secondary one, it will lead to the micro-circulation barrier, and the renal insufficiency of renal tissues. Insufficiency of blood and oxygen leads to the damage of renal capillary endothelial cells. Once the renal capillary endothelial cells are damaged, inflammatory cells will begin infiltration, and release inflammatory medium such as IL-1、TNF—α,etc. At the moment, the pathological damage will lead to the inflammatory reaction. Kidney is on pathological condition. The renal glomerular basilar membrane will have a series of changes. Charge barrier will be damaged. The glycoprotein on the filtration membrane diminishes or disappears, both of which will lead the filtration amount of plasma protein which has negative charge to decrease. So in clinic, protein in urine comes into being.