What is the key distinguishing feature of nephrotic syndrome?

The key distinguishing feature of nephrotic syndrome is the presence of significant proteinuria, specifically greater than 3.5 grams per day. This high level of proteinuria results from increased permeability of the glomerular filtration barrier, often due to underlying conditions such as minimal change disease, membranous nephropathy, or focal segmental glomerulosclerosis. The substantial loss of protein through the urine leads to low serum albumin levels, which can cause a range of clinical consequences, including edema and hyperlipidemia.

While hyperlipidemia is indeed associated with nephrotic syndrome due to the liver's compensatory response to low serum protein levels, it is not the defining characteristic. Similarly, edema, which can occur in various parts of the body (not limited to the lower extremities), is a common symptom, but again, it is not the hallmark of the syndrome itself. Acute kidney injury may occur in certain types of kidney disease but is not a defining feature of nephrotic syndrome, as patients can have normal renal function despite severe proteinuria. Thus, the significant and specific proteinuria greater than 3.5 grams per day is what primarily characterizes nephrotic syndrome.