PLASMA COMPOSITION IN THE NEPHROTIC SYNDROME

The nephrotic syndrome is a consequence of urinary loss of intermediat e sized plasma proteins and the resulting homeostatic responses to tho se losses. Plasma protein composition is changed greatly. Intermediate sized proteins, including albumin, transferrin, IgG, hormone binding proteins, and low molecular weight inhibitors of the clotting cascade, are lost in the urine and their concentration in plasma reduced. Synt hesis of many proteins secreted by the liver is increased either at th e level of transcription or posttranscriptionally. Synthesis of severa l liver-derived proteins is increased in the absence of their urinary loss, suggesting that hypoalbuminemia or reduced plasma oncotic pressu re (pi) stimulates the production or reduces the rate of catabolism of these proteins. Their plasma levels, including those of lipoproteins and elements of the coagulation cascade, are increased. Plasma pi fall s and plasma viscosity increases because of the replacement of interme diate sized plasma proteins by larger ones. The plasma concentration o f several proteins lost in the urine but not secreted by the liver, su ch as erythropoietin and IgG, are not defended by increased synthesis, suggesting that increased synthesis of plasma proteins is primarily c onfined to the liver. Loss of both liver-derived and nonliver-derived proteins may cause reduced immunity, anemia, and deficiency syndromes. Urinary loss of albumin alone is not responsible for decreased plasma pi. The relationship between plasma protein concentration and pi is g reatly disturbed in nephrotic rats. In contrast, the relationship betw een pi and plasma protein concentration is nearly the same in rats wit h hereditary analbuminemia (NAR) and normal rats, despite the absence of albumin from the plasma of NAR. When proteinuria is induced in NAR the relationship between plasma protein concentration and pi becomes i dentical to that in nephrotic animals, although no albumin was lost in the urine of NAR.