Plasma Composition in the Nephrotic Syndrome

Abstract

The nephrotic syndrome is a consequence of urinary loss of intermediate sized plasma proteins and the resulting homeostatic responses to those 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. Synthesis of many proteins secreted by the liver is increased either at the level of transcription or posttranscriptionally. Synthesis of several liver-derived proteins is increased in the absence of their urinary loss, suggesting that hypoalbuminemia or reduced plasma oncotic pressure (Π) 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 Πfalls and plasma viscosity increases because of the replacement of intermediate sized plasma proteins by larger ones. The plasma concentration of several proteins lost in the urine but not secreted by the liver, such as erythropoietin and IgG, are not defended by increased synthesis, suggesting that increased synthesis of plasma proteins is primarily confined to the liver. Loss of both liver-derived and non-liver-derived proteins may cause reduced immunity, anemia, and deficiency syndromes. Urinary loss of albumin alone is not responsible for decreased plasma Π. The relationship between plasma protein concentration and Πis greatly disturbed in nephrotic rats. In contrast, the relationship between Πand plasma protein concentration is nearly the same in rats with 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 Πbecomes identical to that in nephrotic animals, although no albumin was lost in the urine of NAR.

Searching biomarker candidates in serum using multidimensional native chromatography. II Method evaluation with Alport syndrome and severe inflammation

“…2 (region 2) by altered levels of other proteins that coelute with transferrin. Gross alterations of serum protein composition that have been reported with nephrotic syndrome were used to confirm the reliability of the method, i.e., the decrease of a panel of intermediate molecular-weight proteins [31] such as immunoglobulins (Fig. 2) and albumin, and the regulatory increase of transferrin [32,33] and ␣-2-macroglobulin [34].…”

Body Fluid Dynamics

“…61 Inflammatory hypoalbuminemia behaves similarly as α 1 and α 2 fraction—the acute phase proteins—dramatically rise, but differs as the β fraction is unchanged and the γ fraction often increases with chronicity. 62 Thus, globulin osmotic efficiency improves but slightly less compared to analbuminemia with a fall in globulin MW av from ~ 150 kD to ~ 120 kD (see supplemental material).…”

Increased cyclosporine bioavailability induced by experimental nephrotic syndrome in rats

“…Among the most important responses are the hypoalbuminemia and the over-production of lipoproteins and other lipids by the liver, thus greatly changing the plasma composition (Kaysen 1993).…”