Question

What happens to the kidney's membrane filters during proteinuria that allows large moleculars to be found in the urine.

Answer 1

This is a biology question, however, I think this has to do with the functioning of filtration membrane.

When the filtration membrane is not functioning properly, it ceases to be an effective barrier. What then occurs is proteinuria, an abnormal accumulation of protein in the urine. A very small amount of protein gets filtered normally, but this is almost completely reabsorbed in the proximal tubule by endocytosis. If protein is detected in the urine, it usually means that there is a breakdown in the filtration barrier.

There are a number of ways that the filtration membrane can be damaged.  Congenital proteinuria is a rare, inherited form of kidney disease. Congenital proteinuria is caused by genetic mutations that disrupt key structural proteins in the slit diaphragm.

Acquired disorders may also disrupt the structure of the podocyte foot processes and filtration slits and cause proteinuria. The foot processes retract and the podocytes make broad flat contacts with the basement membrane, a condition known as podocyte effacement. The major disorders that disrupt the filtration barrier are diabetes mellitus, hypertension, and glomerulonephritis. In diabetes mellitus, hyperglycemia and/or reduced insulin signaling trigger a set of changes in the filtration membrane that cause a loss of selectivity and result in proteinuria. Hypertension is damaging because the high pressure in the glomerular capillaries damages the filtration membrane. In glomerulonephritis, there is inflammatory damage to the filtration membrane due to immunological attack.

When proteinuria is severe (greater than 3.5g/day), it is called nephrotic syndrome. Nephrotic syndrome consists of a set of signs and symptoms, and may occur as a consequence of any of the various diseases that affect the filtration membrane. Excessive proteinuria causes a low level of protein in the plasma. This combined with sodium retention leads to edema. Other signs of nephrotic syndrome are hyperlipidemia and hypertension.

The degree of proteinuria is a good predictor for the progression of chronic renal disease. This is due to the fact that high levels of protein in the filtrate have a pathogenic effect on the renal tubules. Increased endocytosis of protein by renal tubular cells ultimately stimulates inflammation and fibrosis, and leads to the loss of nephrons.

Because of this pathogenic effect of filtered protein, treatments that decrease proteinuria will have a renoprotective effect. Good control of blood pressure is also important. Several major studies have shown that drugs that block the renin-angiotensin-aldosterone system (RAAS) (ACE inhibitors, angiotensin II receptor blockers and the direct renin inhibitor, aliskiren) are particularly effective at reducing proteinuria. These drugs appear to be helpful even beyond their effect on blood pressure, and this is because of the specific effects of angiotensin II within the kidney. One effect is that the efferent arteriole vasoconstricts more in response to angiotensin II, and so blocking the RAAS prevents excessive pressure in the glomerular capillaries. Another is that angiotensin II causes changes in the renal corpuscle that affect the permeability and selectivity of the filtration membrane.

Hope this helps