Antenatal Membranous Glomerulonephritis Due to Anti–Neutral Endopeptidase Antibodies

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Abstract
Membranous glomerulonephritis, a major cause of the nephrotic syndrome and chronic renal insufficiency, is associated with a wide spectrum of infections, cancers, autoimmune diseases, and drugs. The condition is characterized by an accumulation of immune deposits on the outer aspect of the glomerular basement membrane, but the target antigens have not been identified. Major contributions to our current understanding of the disease come from Heymann's nephritis, a rat model of membranous glomerulonephritis induced by immunization with an antigenic fraction of the renal brush border.1 Studies of this experimental rat model led to the identification of megalin, a unique constitutive antigen expressed on the podocyte.2,3 Although megalin has been found in human proximal tubules, it has not been found in human glomeruli or in immune deposits in patients with membranous glomerulonephritis.4 Dipeptidyl-peptidase IV and neutral endopeptidase are two other antigens shared by the brush border and podocytes that are involved in the formation of immune deposits in animal models; these two proteins are expressed on the human podocyte.5,6