If proteinuria is of sufficient amount, and persists for long enough, then a series of consequences arises which is called the nephrotic syndrome. The most notable consequence of massive proteinuria is salt and water retention leading to edema formation. This edema is found in association with proteinuria usually greater than 3.5 g/day, accompanied by hypoalbuminemia, usually less than 25 g/l. The underlying disease is usually a glomerulonephritis, albeit in rare situations severe renal artery stenosis can lead to proteinuria by hyperfiltration. Two theories have been proposed. In the classical "underfill" theory edema is considered to be secondary to salt retention resulting from renal hypoperfusion. According to this theory the primary event is the decrease in plasma volume due to the diminution of plasma oncotic pressure resulting from hypoalbuminemia, causing transfer of fluid from the plasma to the interstitial space "underfilling" the blood compartment and resulting to secondary renal sodium retention. This mechanism applies mainly to the nephrotic syndrome associated with minimal change disease observed in children. By contrast, in most adults with the nephrotic syndrome due to minimal change disease or other glomerular lesions such as membranous or proliferative glomerulonephritis, an initial plasma volume expansion is observed. Therefore, the primary event responsible for the sodium retention is a renal intrinsic excretory defect, which leads to extracellular fluid expansion and edema formation. Therapy is specific for the specific glomerular disease and symptomatic for the edema (diuretics), anticoagulation therapy for prevention of venous thrombosis and embolism, antibiotics for infections, and most of all, omission of triggering factors such as specific xenobiotics.