Nephrotic Syndrome—Excretion of Protein in the Urine Because of Increased Glomerular Permeability
Many patients with kidney disease develop the nephrotic syndrome, which is characterized by loss of large quantities of plasma proteins into the urine. In some instances, this occurs without evidence of other major abnormalities of kidney function, but more often it is associated with some degree of renal failure.
The cause of the protein loss in the urine is increased permeability of the glomerular membrane. Therefore, any disease that increases the permeability of this mem-brane can cause the nephrotic syndrome. Such diseases include (1) chronic glomerulonephritis, which affects primarily the glomeruli and often causes greatly increased permeability of the glomerular membrane; (2) amyloidosis, which results from deposition of an abnormal proteinoid substance in the walls of the blood vessels and seriously damages the basement membrane of the glomeruli; and (3) minimal change nephrotic syn-drome, which is associated with no major abnormalityin the glomerular capillary membrane that can be detected with light microscopy. As discussed, minimal change nephropathy has been found to be associated with loss of the negative charges that are normally present in the glomerular capillary basement membrane. Immunologic studies have also shown abnormal immune reactions in some cases, suggesting that the loss of the negative charges may have resulted from antibody attack on the membrane. Loss of normal negative charges in the basement membrane of the glomerular capillaries allows proteins, especially albumin, to pass through the glomerular membrane with ease because the negative charges in the basement membrane normally repel the negatively charged plasma proteins.
Minimal change nephropathy can occur in adults, but more frequently it occurs in children between the ages of 2 and 6 years. Increased permeability of the glomeru-lar capillary membrane occasionally allows as much as 40 grams of plasma protein loss into the urine each day, which is an extreme amount for a young child. There-fore, the child’s plasma protein concentration often falls below 2 g/dl, and the colloid osmotic pressure falls from a normal value of 28 to less than 10 mm Hg. As a con-sequence of this low colloid osmotic pressure in the plasma, large amounts of fluid leak from the capillaries all over the body into most of the tissues, causing severe edema.