Cause of nephrotic proteinuria
Proteinuria is a typical symptom of chronic kidney disease, the causes of albuminuria and glomerular barrier function has a close relationship. Proteinuria, glomerular capillaries are composed of three layers, from the inside layer of endothelial cells, respectively, the base film and the epithelial cell layer. As the cells are distributed in three layers of filter pore sizes and negative charge, so the barrier function of glomerular capillary can be divided in two, the mechanical barrier – barrier filter holes and the charge – a negative charge.
There are three main mechanisms to cause proteinuria:
Due to disease in glomerulus
Because of increased quantity of proteins in serum (overflow proteinuria)
Due to low reabsorbtion at proximal tubule (fanconi)
Proteinuria can also be caused by certain biological agents, such as bevacizumab (Avastin) used in cancer treatment.
1, the mechanical barrier – Scleral
Glomerular filtration barrier from the inside out by three components:
① Inner layer is the capillary endothelial cells. Endothelial cells have many small holes 50-100nm in diameter, called fenestrae (fenestration). Water, a variety of solutes and macromolecules can freely through the fenestrae of protein; but it prevents the blood cells through, playing the role of blood cell barrier.
② Middle of the base non-cellular membrane, was micro fiber network structure. Larger plasma molecules, such as basement membrane proteins cannot. Glomerular basement membrane is the filtration of protein molecules to prevent a major barrier.
③ Outer layer is the glomerular epithelial cells. Epithelial cells foot processes, cross-cutting fissure between the foot processes. Fissure cracks on a layer of membrane filtration (filtration slit membrane), membrane 4-14nm in diameter holes, which can prevent from the inside, the two proteins through the filter out of the macromolecules, is the final filtration barrier. Endothelial cells, basement membrane and the membrane constitute the fractured glomerular filtration membrane. Filtration membrane filtration channels of different sizes, so the small molecules can easily pass, the larger the effective radius of the material only through the larger channels, in general, the effective radius of less than 1.8nm material, can be completely filtered. Effective radius is larger than 3.6nm macromolecules, such as albumin (molecular weight of about 69,000) is almost totally filtered.
2, the charge barrier – the negative charge
Filtration membrane contains many layers of material with a negative charge, so the permeability of the membrane filtration is filtration material is also determined by the charge. The exclusion of the negatively charged material with negatively charged plasma proteins, limiting their filtration. Although the effective radius of serum albumin 3.5nm, but because of its negative charge, it is difficult through the filtration membrane. When a variety of pathological damage (including primary and secondary injury) on the kidneys, can cause partial damage to the kidney microcirculation, promote kidney (functional renal units) ischemia and hypoxia. Because ischemia, hypoxic injury of the glomerular capillary endothelial cells. Glomerular capillary endothelial cells, once damaged, it will attract circulating inflammatory cell infiltration, and release of inflammatory mediators of disease (IL-1, TNF – α, etc.) can cause pathological damage at this time impaired renal inflammatory response. Kidney in the pathological state, glomerular basement membrane (GBM) will be a series of changes: the increase or closed pore filtration, GBM fracture, the charge barrier damage, kidney permeability-increasing, negatively charged membrane filtration of sugar proteins decreased or disappeared, will lead to negatively charged than the normal plasma protein significantly increased filtration. Therefore, the formation of clinical proteinuria.
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