This is associated with marked thickening of GBM and decreased number of filtration slits from podocyte broadening. Second, nephrotic syndrome associated with renal Na retention due to decreased GFR and increased distal tubular Na reabsorption. Na reabsorption is associated with resistance to atrial natriuretic peptide from degradation of its second messenger cGMP by increased phosphodiesterase activity. The signals that cause these abnormalities are unknown. NS associated with increased fractional rate albumin catabolism but decreased absolute catabolic rate.
Severity correlates with degree of hypoalbuminemia.
Pathophysiology - Hypoalbuminemia via low plasma oncotic pressure causes increased hepatic synthesis of lipoproteins, esp apoprotein B, and cholesterol. Protective HDL are lost in urine. Decreased clearance of VLDL due in part to decreased lipoprotein lipase activity. Decrease in clearance correlates better with renal albumin clearance than with plasma oncotic pressure suggesting loss of a factor involved in VLDL metabolism. In addition, increased levels of fibrinogen and evidence of activation of both fibrin formation and degradation are found.