The Mechanism of the Formation of Proteinuria

Due to the filtration function of glomerulus and the resorption function of renal tubules, there is little amount of the protein (referring to proteinuria with small molecular weight) in the urine of healthy people (less than 150mg per day). In the protein qualitative check, the result is negative. When the amount of protein in the urine increases, it can be detected by the urine routine test and it is called proteinuria. If the protein amount is more than 3.5g/24h, it is called severe proteinuria.

How does proteinuria form? What is the mechanism of the formation of proteinuria?
Proteinuria is the classical symptom of chronic kidney disease. The reason of the formation of proteinuria is related to the barrier function of glomerulus. Glomerulus blood capillaries are constituted by three layers. From inside to outside, they are respectively endothelial cell layer, basement membrane layer and epithelial cell layer. On the three layers, there located numerous filtration pores with different diameter and there is negative charge, so the barrier function of glomerulus blood vessels can be divided into mechanical barrier function and charge barrier function.

First, the mechanical barrier function-filtration pores

The barrier function of glomerulus is constituted by three layers from inside to outside:

1, the inner layer is the endothelial cells of blood capillary. There are numerous pores with 50-100nm diameter in the endothelial cells which is called fenestration. Water, various kinds of solute and macromolecular proteins can pass the fenestrations freely, while these fenestrations can block the blood corpuscle, which play a barrier function of blood corpuscle.

2, the middle layer is the non-cell basement memebrane layer, which presents the microfiber net structure. The macromolecular substances in the plasma, such as protein, can ‘t pass this layer. So the basement membrane is the main barrier of gomerulus to prevent the macromolecular protein from being filtrated out.

3, the outer layer is the epithelial cell layer. There are podocyticprocesses on the epithelial cells. The criss-crossed podocyticprocesses form slits. And there is a layer of filtration slit membrane on the slits. On this membrane, there are pores with 4-14nm diameter which can block the protein filtrated by the former layers, so it is the last barrier of filtration. The three layers constitute the filtration barrier of the glomerulus. These pores of different diameters only allow the micro-molecular substances to pass. Generally speaking, substances with effective radius less than 1.8nm can all be filtrated. Substances with effective radius more than 3.6nm, such as plasma albumin (the molecular weight is about 69000), can’t be filtrated completely.

Second, charge barrier function-negative charge

There are various kinds of substances carrying negative charges, so the permeability of the filtration membrane also related to the charges that carried by different substances. These substances carrying negative charges will repel the plasma protein which also carrying negative charges, so this can prevent the protein from passing.

However, when various pathology damages act on the kidneys, they will lead to the focal microcirculatory disturbance of the kidneys, which will cause the ischemia and anemia of the renal tissues (renal functional units). Then, the capillary endothelial cells will be damaged because of the ischemia and anemia. Once the capillary endothelial cells are damaged, this will attract the inflammatory cell infiltration in the blood circulation and they will release pathogenic mediums (IL-1、TNF—α, etc). at this time, the pathology damage will cause the inflammatory reaction of the damaged kidneys.


As for the kidneys in the pathological state, there are a series of changes of glomerulus basement membrane: the filtration pores will enlarge or block; glomerulus basement membrane will breakdown; charge barrier will be damaged; the permeability will enhance; the glycoprotein carrying negative charges in the filtration membrane will decrease or disappear. All of these will lead to the amount of protein that is filtrated increase obviously. This is the mechanism of the formation of proteinuria.