Why There is Massive Proteinuria in Nephrotic Syndrome

Massive proteinuria (more than 3.5g/d) is the significant sign of nephrotic syndrome and the leaked protein in urine is mainly albumin and there are other plasma proteins.

The increased permeability of glomerular basement membrane is the root cause of proteinuria. When the charge barrier and mechanical barrier especially the charge barrier is damaged, the plasma proteins will pass through the membrane and when the amount exceeds the re-absorption ability of the renal tubules, there will be protein leakage in the urine.

The glomerular filtration rate (GFR), concentration of plasma protein as well as the protein intake has direct influence on the severity of proteinuria. When GFR decreases, proteinuria will decrease; in case of severe hypoalbuminemia, the protein in urine will increase and high-protein diet can further aggravate proteinuria. However it is not accurate to measure daily protein quantity, further tests such as albumin clearance can be done.

Long term proteinuria will cause severe hypoalbuminemia (the serum protein is less than 30g/l) which is the second necessary feature of nephrotic syndrome. In case of nephrotic syndrome, the synthesis of protein in the liver will increase and only when the compensatory ability of the liver can not make up the protein loss can there be hypoalbuminemia. That is why there is sometimes inconsistence between low serum protein and protein leakage in the urine.

The intake of ACEI (angiotensin converting enzyme inhibitor) can inhibit the leakage of protein in urine and there will be obvious increase of serum protein. However there is one thing that needs to be noted. In case of hypoalbuminemia, the combination of medicines and albumin will decrease and the free medicines in the blood will increase and this may increase the toxicity of the medicines to the body. What is more, ACEI can only suppress the proteinuria without solving the root problems, that is why proteinuria will recur again and again and the illness condition will continue to deteriorate. To treat proteinuria from the root, the damaged glomerular basement membrane must be repaired.