The pathophysiology of edema formation in the nephrotic syndrome

The mechanism of edema formation in the nephrotic syndrome has long been a source of controversy. In this review, through the construct of Starling's forces, we examine the roles of albumin, intravascular volume, and neurohormones on edema formation and highlight the evolving literature on the role of primary sodium absorption in edema formation. We propose that a unifying mechanism of sodium retention is present in the nephrotic syndrome regardless of intravascular volume status and is due to the activation of epithelial sodium channel by serine proteases in the glomerular filtrate of nephrotic patients. Finally, we assert that mechanisms in addition to sodium retention are likely operant in the formation of nephrotic edema.