Nephrotic syndrome is described by a group of signs including massive proteinuria (defined as a daily loss of 3.5 gm or more of urinary protein), hyperlipidemia, generalized edema, and hypoalbuminemia, which results from renal pathology. It may present with renal vein thrombosis.
On light microscopy, the glomeruli typically exhibit uniform, diffuse thickening of the capillaries and glomerular basement membrane.
On electron microscopy, the thickening is seen to be caused by irregular dense immune complex deposition between the basement membrane and podocytes. The basement membrane between the deposits appear as irregular spikes and over time, the spikes thicken to produce dome-like protrusions over the immune deposits. This is commonly described as having a “spike-and-dome” appearance with subepithelial deposits.
Immunofluorescence studies on biopsy samples demonstrate a granular pattern of IgG and complement staining of the glomerular basement membrane.
Primary membranous nephropathy is the most common form. Patients often test positive for autoantibodies directed against the phospholipase A2 receptor, a transmembrane receptor present in podocytes.
Membranous glomerulonephritis can result after exposure to various types of medications. NSAIDs such as ibuprofen or diclofenac are a potential cause of membranous glomerulonephritis. If this is suspected, the NSAID should be stopped.
Nephrotic syndrome can either be primary, or secondary to a systemic disease or to medication use. For example, the use of medicines containing gold, which was used in the past for rheumatoid arthritis, may result in membranous nephropathy. Another causative medication is penicillamine.
Another secondary cause of membranous nephropathy is the presence of a solid tumor elsewhere in the body, particularly carcinomas of the lung and colon, along with melanoma. The pathophysiology may involve deposition of tumor antigens within the glomerulus.
Patients with chronic hepatitis B and hepatitis C can develop membranous nephropathy. Although both have been implicated as etiologic agents, hepatitis B has a stronger association with membranous nephropathy, while hepatitis C is more strongly associated with membranoproliferative glomerulonephritis. The pathophysiology involves deposition of viral antigens within the glomerulus.
Lupus is a systemic autoimmune disease which can result in different forms of renal disease. Membranous nephropathy is one such form, secondary to deposition of antibodies and complement within the glomerulus.
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