Nephrotic syndrome is defined by the clinical findings of heavy proteinuria, hypoalbuminemia, edema (often to the point of frank anasarca), and hyperlipidemia. Many causes of nephrotic syndrome exist, and the most likely cause varies by age. Nephrotic syndrome may be the result of an underlying systemic disease, or it may manifest as a primary idiopathic renal disorder. Examples of causes of primary and secondary nephrotic syndrome in children are listed in BOX 297-1. The overall outcome of nephrotic syndrome depends on the etiology and ranges from complete remission with no long-term sequelae to inexorable progression to end-stage renal failure. Newer treatments offer alternatives for patients with resistant forms of nephrotic syndrome or who experience significant side effects from first-line treatments, although such treatments themselves carry the potential for significant side effects.